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Greatly impacted by their environment, microglia go through rapid changes in cell shape, gene expression, and functional behavior during states of infection, trauma, and neurodegeneration. Aging also has a profound effect on microglia, leading to chronic inflammation and an increase in the brain\u2019s susceptibility to neurodegenerative processes that occur in Alzheimer\u2019s disease. Despite the scientific community\u2019s growing knowledge in the field of neuroinflammation, the overall success rate of drug treatment for age-related and neurodegenerative diseases remains incredibly low. Potential reasons for the lack of translation from animal models to the clinic include the use of a single species model, an assumption of similarity in humans, and ignoring contradictory data or information from other species. To aid in the selection of validated and predictive animal models and to bridge the translational gap, this review evaluates similarities and differences among species in microglial activation and density, morphology and phenotype, cytokine expression, phagocytosis, and production of oxidative species in aging and Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/cells10051138","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T21:32:46Z","timestamp":1620595966000},"page":"1138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":120,"title":["Microglia in Aging and Alzheimer\u2019s Disease: A Comparative Species Review"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9084-9539","authenticated-orcid":false,"given":"Melissa K.","family":"Edler","sequence":"first","affiliation":[{"name":"Department of Anthropology, School of Biomedical Sciences, Brain Health Research Institute, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isha","family":"Mhatre-Winters","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, College of Arts and Sciences, Kent State University, Kent, OH 44240, USA"},{"name":"Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason R.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.tins.2012.11.007","article-title":"Microglia: Actively surveying and shaping neuronal circuit structure and function","volume":"36","author":"Wake","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1016\/j.neurobiolaging.2007.04.013","article-title":"Neocortical glial cell numbers in human brains","volume":"29","author":"Pelvig","year":"2008","journal-title":"Neurobiol. Aging"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1152\/physrev.00011.2010","article-title":"Physiology of Microglia","volume":"91","author":"Kettenmann","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1126\/science.1110647","article-title":"Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo","volume":"308","author":"Nimmerjahn","year":"2005","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-2094-1-14","article-title":"Microglia and neuroinflammation: A pathological perspective","volume":"1","author":"Streit","year":"2004","journal-title":"J. Neuroinflamm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.neurobiolaging.2005.08.008","article-title":"Inflammation, the complement system and the diseases of aging","volume":"26","author":"McGeer","year":"2005","journal-title":"Neurobiol. Aging"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3798","DOI":"10.1016\/j.febslet.2011.08.033","article-title":"Role of microglia in CNS inflammation","volume":"585","author":"Graeber","year":"2011","journal-title":"FEBS Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.expneurol.2013.05.014","article-title":"A survey from 2012 of evidence for the role of neuroinflammation in neurotoxin animal models of Parkinson\u2019s disease and potential molecular targets","volume":"256","author":"Ramsey","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_9","first-page":"pe29","article-title":"Immunotherapy for Alzheimer\u2019s Disease","volume":"27","author":"McGeer","year":"2004","journal-title":"Sci. Aging Knowl. Environ."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.brainres.2005.08.029","article-title":"Anti-inflammatory mechanism is involved in ethyl pyruvate-mediated efficacious neuroprotection in the postischemic brain","volume":"1060","author":"Kim","year":"2005","journal-title":"Brain Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0304-3940(87)90696-3","article-title":"Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR","volume":"79","author":"McGeer","year":"1987","journal-title":"Neurosci. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0006-8993(00)02984-X","article-title":"Expression of CD40 in the brain of Alzheimer\u2019s disease and other neurological diseases","volume":"885","author":"Togo","year":"2000","journal-title":"Brain Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jneuroim.2017.04.007","article-title":"Staining of HLA-DR, Iba1 and CD68 in human microglia reveals partially overlapping expression depending on cellular morphology and pathology","volume":"309","author":"Hendrickx","year":"2017","journal-title":"J. Neuroimmunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/0306-4522(92)90500-2","article-title":"Turnover of resident microglia in the normal adult mouse brain","volume":"48","author":"Lawson","year":"1992","journal-title":"Neuroscience"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.bbi.2011.11.006","article-title":"Age related changes in microglial phenotype vary between CNS regions: Grey versus white matter differences","volume":"26","author":"Hart","year":"2012","journal-title":"Brain Behav. Immun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/glia.440070111","article-title":"Altered antigen expression of microglia in the aged rodent CNS","volume":"7","author":"Perry","year":"1993","journal-title":"Glia"},{"key":"ref_17","first-page":"S83","article-title":"Litter size, age-related memory impairments, and microglial morphological changes in the rat lateral septum analyzed by three dimensional reconstruction","volume":"61","author":"Viana","year":"2013","journal-title":"Glia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.neuron.2013.05.007","article-title":"Microglia as Dynamic and Essential Components of the Amyloid Hypothesis","volume":"78","author":"Gandy","year":"2013","journal-title":"Neuron"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nri3705","article-title":"Innate immune activation in neurodegenerative disease","volume":"14","author":"Heneka","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nrneurol.2014.38","article-title":"Microglial priming in neurodegenerative disease","volume":"10","author":"Perry","year":"2014","journal-title":"Nat. Rev. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nrd3375","article-title":"Phase III and submission failures: 2007\u20132010","volume":"10","author":"Arrowsmith","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1002\/glia.10319","article-title":"Dystrophic microglia in the aging human brain","volume":"45","author":"Streit","year":"2004","journal-title":"Glia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.tins.2014.02.005","article-title":"Response to Watkins and Hutchinson","volume":"37","author":"Smith","year":"2014","journal-title":"Trends Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1111\/acel.12149","article-title":"Homeostatic and injury-induced microglia behavior in the aging brain","volume":"13","author":"Hefendehl","year":"2014","journal-title":"Aging Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/j.1474-9726.2010.00660.x","article-title":"Age-related alterations in the dynamic behavior of microglia","volume":"10","author":"Damani","year":"2011","journal-title":"Aging Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1093\/icb\/icp009","article-title":"Immune and behavioral consequences of microglial reactivity in the aged brain","volume":"49","author":"Wynne","year":"2009","journal-title":"Integr. Comp. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1002\/glia.20468","article-title":"Microglia derived from aging mice exhibit an altered inflammatory profile","volume":"55","author":"Sierra","year":"2007","journal-title":"Glia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.exger.2017.01.027","article-title":"Aging leads to altered microglial function that reduces brain resiliency increasing vulnerability to neurodegenerative diseases","volume":"94","author":"Bickford","year":"2017","journal-title":"Exp. Gerontol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Koellhoffer, E.C., McCullough, L.D., and Ritzel, R.M. (2017). Old Maids: Aging and Its Impact on Microglia Function. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040769"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.neurobiolaging.2010.09.016","article-title":"Microglial activation in healthy aging","volume":"33","author":"Schuitemaker","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.neuroimage.2011.02.020","article-title":"Age and disease related changes in the translocator protein (TSPO) system in the human brain: Positron emission tomography measurements with [11C]vinpocetine","volume":"56","author":"Vas","year":"2011","journal-title":"NeuroImage"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.neuroimage.2013.09.021","article-title":"Neuroinflammation in healthy aging: A PET study using a novel Translocator Protein 18kDa (TSPO) radioligand, [18F]-FEPPA","volume":"84","author":"Suridjan","year":"2014","journal-title":"NeuroImage"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/00005072-199702000-00004","article-title":"Microglial cell activation in aging and Alzheimer disease: Partial linkage with neurofibrillary tangle burden in the hippocampus","volume":"56","author":"DiPatre","year":"1997","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3389\/fnagi.2019.00094","article-title":"Activated Microglia in Cortical White Matter Across Cognitive Aging Trajectories","volume":"11","author":"Gefen","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_35","first-page":"1","article-title":"Evidence of tau hyperphosphorylation and dystrophic mi-croglia in the common marmoset","volume":"8","author":"Fuchs","year":"2016","journal-title":"Front. Aging Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.neurobiolaging.2008.07.006","article-title":"Age-related changes in glial cells of dopamine midbrain subregions in rhesus monkeys","volume":"31","author":"Kanaan","year":"2010","journal-title":"Neurobiol. Aging"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1002\/glia.20686","article-title":"The neuroglial population in the primary visual cortex of the aging rhesus monkey","volume":"56","author":"Peters","year":"2008","journal-title":"Glia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.neurobiolaging.2017.07.006","article-title":"Aged chimpanzees exhibit pathologic hallmarks of Alzheimer\u2019s disease","volume":"59","author":"Edler","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.bbi.2016.01.006","article-title":"Glial cell morphological and density changes through the lifespan of rhesus macaques","volume":"55","author":"Robillard","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s11357-017-9965-y","article-title":"Microglia activation and phagocytosis: Relationship with aging and cognitive impairment in the rhesus monkey","volume":"39","author":"Shobin","year":"2017","journal-title":"GeroScience"},{"key":"ref_41","first-page":"384","article-title":"Effects of aging on the neuroglial cells and pericytes within area 17 of the rhesus monkey cerebral cortex","volume":"229","author":"Peters","year":"1991","journal-title":"Anat. Rec. Adv. Integr. Anat. Evol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1097\/00001756-199406020-00016","article-title":"Effects of ageing on microglia in the normal rat brain: Immunohistochemical observations","volume":"5","author":"Ogura","year":"1994","journal-title":"NeuroReport"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0306-4522(98)00334-0","article-title":"The mosaic of brain glial hyperactivity during normal ageing and its attenuation by food restriction","volume":"89","author":"Morgan","year":"1999","journal-title":"Neuroscience"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Yegla, B., Boles, J., Kumar, A., and Foster, T.C. (2021). Partial microglial depletion is associated with impaired hippocampal synaptic and cognitive function in young and aged rats. Glia, 1\u201321.","DOI":"10.1002\/glia.23975"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3389\/fnagi.2018.00146","article-title":"Cell-Type Specific Changes in Glial Morphology and Glucocorticoid Expression During Stress and Aging in the Medial Prefrontal Cortex","volume":"10","author":"Chan","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.neuroscience.2018.02.028","article-title":"Stereological Analysis of Microglia in Aged Male and Female Fischer 344 Rats in Socially Relevant Brain Regions","volume":"377","author":"Perkins","year":"2018","journal-title":"Neuroscience"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/BF01098730","article-title":"Neuroglial cells in the cerebral cortex of rats from young adulthood to old age: An electron microscope study","volume":"3","author":"Vaughan","year":"1974","journal-title":"J. Neurocytol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1097\/01.jnen.0000202887.22082.63","article-title":"Microglia in the Aging Brain","volume":"65","author":"Conde","year":"2006","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0197-4580(97)00169-3","article-title":"Age-Related Activation of Microglia and Astrocytes: In Vitro Studies Show Persistent Phenotypes of Aging, Increased Proliferation, and Resistance to Down-Regulation","volume":"19","author":"Rozovsky","year":"1998","journal-title":"Neurobiol. Aging"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1292\/jvms.69.1131","article-title":"Age-Related Changes in Ionized Calcium-Binding Adapter Molecule 1 Immunoreactivity and Protein Level in the Gerbil Hippocampal CA1 Region","volume":"69","author":"Choi","year":"2007","journal-title":"J. Vet. Med. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"206","DOI":"10.3389\/fnmol.2017.00206","article-title":"Increased White Matter Inflammation in Aging- and Alzheimer\u2019s Disease Brain","volume":"10","author":"Raj","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S0006-8993(02)03475-3","article-title":"Age and gender effects on microglia and astrocyte numbers in brains of mice","volume":"956","author":"Mouton","year":"2002","journal-title":"Brain Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/glia.22287","article-title":"Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices","volume":"60","author":"Tremblay","year":"2012","journal-title":"Glia"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0197-4580(98)00088-8","article-title":"Stereological analysis of astrocyte and microglia in aging mouse hippocampus","volume":"19","author":"Long","year":"1998","journal-title":"Neurobiol. Aging"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s00441-012-1537-y","article-title":"Distribution of microglia in the postnatal murine nigrostriatal system","volume":"351","author":"Sharaf","year":"2012","journal-title":"Cell Tissue Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.mad.2007.01.005","article-title":"Age-related changes of astorocytes, oligodendrocytes and microglia in the mouse hippocampal CA1 sector","volume":"128","author":"Hayakawa","year":"2007","journal-title":"Mech. Ageing Dev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/1742-2094-8-138","article-title":"Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment","volume":"8","author":"VanGuilder","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1111\/j.1471-4159.2011.07630.x","article-title":"Sex differences in microglial colonization of the developing rat brain","volume":"120","author":"Schwarz","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1007\/s11064-007-9584-6","article-title":"Comparison of Ionized Calcium-binding Adapter Molecule 1 Immunoreactivity of the Hippocampal Dentate Gyrus and CA1 Region in Adult and Aged Dogs","volume":"33","author":"Hwang","year":"2008","journal-title":"Neurochem. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1292\/jvms.15-0624","article-title":"The Relation between canine cognitive dysfunction and age-related brain lesions","volume":"78","author":"Ozawa","year":"2016","journal-title":"J. Vet. Med. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jcpa.2009.07.007","article-title":"Parenchymal and Vascular Lesions in Ageing Equine Brains: Histological and Immunohistochemical Studies","volume":"142","author":"Capucchio","year":"2010","journal-title":"J. Comp. Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/nri2015","article-title":"Systemic infections and inflammation affect chronic neurodegeneration","volume":"7","author":"Perry","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1016\/j.neurobiolaging.2015.02.016","article-title":"Age- and location-related changes in microglial function","volume":"36","author":"Ritzel","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3389\/fncel.2013.00022","article-title":"Microglial aging in the healthy CNS: Phenotypes, drivers, and rejuvenation","volume":"7","author":"Wong","year":"2013","journal-title":"Front. Cell. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.4049\/jimmunol.176.3.1402","article-title":"CD40 Expression by Microglial Cells Is Required for Their Completion of a Two-Step Activation Process during Central Nervous System Autoimmune Inflammation","volume":"176","author":"Ponomarev","year":"2006","journal-title":"J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/icb.1997.68","article-title":"The role of CD45 and CD45-associated molecules in T cell activation","volume":"75","author":"Altin","year":"1997","journal-title":"Immunol. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1093\/brain\/awt210","article-title":"Inflammatory components in human Alzheimer\u2019s disease and after active amyloid-\u03b242 immunization","volume":"136","author":"Zotova","year":"2013","journal-title":"Brain"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s004010050792","article-title":"Enlarged and phagocytic, but not primed, interleukin-1\u03b1-immunoreactive microglia increase with age in normal human brain","volume":"95","author":"Sheng","year":"1998","journal-title":"Acta Neuropathol."},{"key":"ref_69","first-page":"1101","article-title":"Detection of HLA-DR on microglia in the human brain is a function of both clinical and technical factors","volume":"136","author":"Mattiace","year":"1990","journal-title":"Am. J. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.neurobiolaging.2016.12.028","article-title":"Rod-shaped microglia morphology is associated with aging in 2 human autopsy series","volume":"52","author":"Bachstetter","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0014-4886(90)90054-V","article-title":"Molecular, cellular, and pathologic characterization of HLA-DR immunoreactivity in normal elderly and Alzheimer\u2019s disease brain","volume":"110","author":"Styren","year":"1990","journal-title":"Exp. Neurol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s00401-009-0556-6","article-title":"Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer\u2019s disease","volume":"118","author":"Streit","year":"2009","journal-title":"Acta Neuropathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1111\/bpa.12456","article-title":"Microglia show altered morphology and reduced arborization in human brain during aging and Alzheimer\u2019s disease","volume":"27","author":"Davies","year":"2016","journal-title":"Brain Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e22956","DOI":"10.1002\/ajp.22956","article-title":"Loss of ferritin-positive microglia relates to increased iron, RNA oxidation, and dystrophic microglia in the brains of aged male marmosets","volume":"81","author":"Fonta","year":"2019","journal-title":"Am. J. Primatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1354\/vp.45-4-531","article-title":"Neuro-pathologic findings in an aged albino gorilla","volume":"45","author":"Serafin","year":"2008","journal-title":"Vet. Pathol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S0197-4580(99)00066-4","article-title":"Increased microglial activation and protein nitration in white matter of the aging monkey","volume":"20","author":"Sloane","year":"1999","journal-title":"Neurobiol. Aging"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0197-4580(97)00168-1","article-title":"Microglial Expression of MHC Class II Increases in Normal Aging of Nonhuman Primates","volume":"19","author":"Sheffield","year":"1998","journal-title":"Neurobiol. Aging"},{"key":"ref_78","first-page":"254","article-title":"The brain\u2019s aging immune system","volume":"1","author":"Streit","year":"2010","journal-title":"Aging Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1096\/fj.05-3776fje","article-title":"Exaggerated neuroinflammation and sickness behavior in aged mice after activation of the peripheral innate immune system","volume":"19","author":"Godbout","year":"2005","journal-title":"FASEB J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.neulet.2005.07.058","article-title":"Macrosialin increases during normal brain aging are attenuated by caloric restriction","volume":"390","author":"Wong","year":"2005","journal-title":"Neurosci. Lett."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1002\/cne.23877","article-title":"Tau hyperphosphorylation in synaptosomes and neuroinflammation are associated with canine cognitive impairment","volume":"524","author":"Smolek","year":"2015","journal-title":"J. Comp. Neurol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1002\/glia.23804","article-title":"Increased oxidative stress, hyperphosphorylation of tau, and dystrophic microglia in the hippocampus of agedTupaia belangeri","volume":"68","author":"Fuchs","year":"2020","journal-title":"Glia"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.cellimm.2012.01.001","article-title":"Aging is associated with circulating cytokine dysregulation","volume":"273","year":"2012","journal-title":"Cell. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.neurobiolaging.2015.10.039","article-title":"The inflammatory markers CRP, IL-6, and IL-10 are associated with cognitive function\u2014Data from the Berlin Aging Study II","volume":"38","author":"Tegeler","year":"2016","journal-title":"Neurobiol. Aging"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"18052","DOI":"10.3402\/pba.v2i0.18052","article-title":"Age-dependent changes in innate immune phenotype and function in rhesus macaques (Macaca mulatta)","volume":"2","author":"Asquith","year":"2012","journal-title":"Pathobiol. Aging Age-Relat. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1006\/cyto.1997.0281","article-title":"Effect of age and hormonal state on cytokine synthesis in the monkey","volume":"10","author":"Kaack","year":"1998","journal-title":"Cytokine"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1742-4933-9-25","article-title":"Immune correlates of aging in outdoor-housed captive rhesus macaques (Macaca mulatta)","volume":"9","author":"Didier","year":"2012","journal-title":"Immun. Ageing"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1093\/ilar.52.1.54","article-title":"The Marmoset as a Model of Aging and Age-Related Diseases","volume":"52","author":"Tardif","year":"2011","journal-title":"ILAR J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1159\/000049025","article-title":"An Age-Related Decline in Interleukin-10 May Contribute to the Increased Expression of Interleukin-6 in Brain of Aged Mice","volume":"9","author":"Ye","year":"2001","journal-title":"Neuroimmunomodulation"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"8904","DOI":"10.1523\/JNEUROSCI.1146-14.2014","article-title":"IL-4 Signaling Drives a Unique Arginase+\/IL-1 + Microglia Phenotype and Recruits Macrophages to the Inflammatory CNS: Consequences of Age-Related Deficits in IL-4R after Traumatic Spinal Cord Injury","volume":"34","author":"Fenn","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"195.e1","DOI":"10.1016\/j.neurobiolaging.2010.05.008","article-title":"Ex vivo cultures of microglia from young and aged rodent brain reveal age-related changes in microglial function","volume":"33","author":"Njie","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1038\/nn.3554","article-title":"The microglial sensome revealed by direct RNA sequencing","volume":"16","author":"Hickman","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0014-4886(03)00057-8","article-title":"Aging and glial responses to lipopolysaccharide in vitro: Greater induction of IL-1 and IL-6, but smaller induction of neurotoxicity","volume":"182","author":"Xie","year":"2003","journal-title":"Exp. Neurol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.bbi.2013.12.018","article-title":"Age-dependent changes on TGF\u03b21 Smad3 pathway modify the pattern of microglial cell activation","volume":"37","author":"Tichauer","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0165-5728(98)00217-3","article-title":"Increased interleukin-6 expression by microglia from brain of aged mice","volume":"93","author":"Ye","year":"1999","journal-title":"J. Neuroimmunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.bbi.2008.09.002","article-title":"Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1\u03b2 and anti-inflammatory IL-10 cytokines","volume":"23","author":"Henry","year":"2009","journal-title":"Brain Behav. Immun."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.bbi.2008.12.008","article-title":"Central inhibition of interleukin-1\u03b2 ameliorates sickness behavior in aged mice","volume":"23","author":"Abraham","year":"2009","journal-title":"Brain Behav. Immun."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bbi.2008.07.002","article-title":"Time course of hippocampal IL-1 \u03b2 and memory consolidation impairments in aging rats following peripheral infection","volume":"23","author":"Barrientos","year":"2009","journal-title":"Brain Behav. Immun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1111\/j.1939-1676.2008.0076.x","article-title":"Cytokine Dysregulation in Aged Horses and Horses with Pituitary Pars Intermedia Dysfunction","volume":"22","author":"McFarlane","year":"2008","journal-title":"J. Vet. Intern. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/agm2.12121","article-title":"Oxidative stress in elderly population: A prevention screening study","volume":"3","author":"Gorni","year":"2020","journal-title":"Aging Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.brainres.2005.11.021","article-title":"Cognitive disturbances in old dogs suffering from the canine counterpart of Alzheimer\u2019s disease","volume":"1069","author":"Rofina","year":"2006","journal-title":"Brain Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev.immunol.20.083001.084359","article-title":"Innate immune recognition","volume":"20","author":"Janeway","year":"2002","journal-title":"Annu. Rev. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1089\/wound.2012.0380","article-title":"Chemokines and Their Receptors Are Key Players in the Orchestra That Regulates Wound Healing","volume":"2","author":"Petreaca","year":"2013","journal-title":"Adv. Wound Care"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"re1","DOI":"10.1126\/sageke.2005.5.re1","article-title":"Lipofuscin and Aging: A Matter of Toxic Waste","volume":"2005","author":"Gray","year":"2005","journal-title":"Sci. Aging Knowl. Environ."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1007\/PL00014168","article-title":"Neuropathology of Alzheimer\u2019s disease: What is new since A. Alzheimer?","volume":"249","author":"Braak","year":"1999","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0167-4943(01)00223-0","article-title":"Sequential histochemical studies of neuronal lipofuscin in human cerebral cortex from the first to the ninth decade of life","volume":"34","author":"Benavides","year":"2002","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1159\/000490908","article-title":"A Sequential Study of Age-Related Lipofuscin Accumulation in Hippocampus and Striate Cortex of Rats","volume":"25","author":"Kushwaha","year":"2018","journal-title":"Ann. Neurosci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1016\/j.neurobiolaging.2005.06.008","article-title":"Differences in the early inflammatory responses to toxin-induced demyelination are associated with the age-related decline in CNS remyelination","volume":"27","author":"Zhao","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Rashed, M.H., Bayraktar, E., Helal, G.K., Abd-Ellah, M.F., Amero, P., Chavez-Reyes, A., and Rodriguez-Aguayo, C. (2017). Exosomes: From Garbage Bins to Promising Therapeutic Targets. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030538"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1189\/jlb.0913485","article-title":"Activated macrophages release microvesicles containing polarized M1 or M2 mRNAs","volume":"95","author":"Garzetti","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1002\/glia.22497","article-title":"Classical and unconventional pathways of vesicular release in microglia","volume":"61","author":"Prada","year":"2013","journal-title":"Glia"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.neuroscience.2018.04.003","article-title":"Cell-to-cell Communication by Extracellular Vesicles: Focus on Microglia","volume":"405","author":"Paolicelli","year":"2019","journal-title":"Neuroscience"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3389\/fnagi.2019.00232","article-title":"Exosome Determinants of Physiological Aging and Age-Related Neurodegenerative Diseases","volume":"11","author":"Fenoglio","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.mad.2017.02.008","article-title":"Exosome-based immunomodulation during aging: A nano-perspective on inflamm-aging","volume":"168","author":"Prattichizzo","year":"2017","journal-title":"Mech. Ageing Dev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1146\/annurev-immunol-041015-055700","article-title":"Antigen Presentation by Extracellular Vesicles from Professional Antigen-Presenting Cells","volume":"36","author":"Lindenbergh","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nri3622","article-title":"Regulation of immune responses by extracellular vesicles","volume":"14","author":"Robbins","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11357-019-00115-w","article-title":"Extracellular vesicles from mesenchymal stem cells reduce microglial-mediated neuroinflammation after cortical injury in aged Rhesus monkeys","volume":"42","author":"Go","year":"2020","journal-title":"GeroScience"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Udeochu, J., Sanchez-Diaz, C., Cai, A., Jovicic, A., and Villeda, A. (2018). Exosome release promotes inflammatory resolution in activated and aged microglia. bioRxiv, 423558.","DOI":"10.1101\/423558"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-018-1204-7","article-title":"Inflammation leads to distinct populations of extracellular vesicles from microglia","volume":"15","author":"Yang","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3389\/fnagi.2017.00012","article-title":"Plasma Exosomes Spread and Cluster Around \u03b2-Amyloid Plaques in an Animal Model of Alzheimer\u2019s Disease","volume":"9","author":"Zheng","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_122","unstructured":"Alzheimer\u2019s Association (2021). Alzheimer\u2019s Disease Facts and Figures: Race, Ethnicity and Alzheimer\u2019s in America, Alzheimer\u2019s Association. Alzheimers Dement."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-011-0910-3","article-title":"National Institute on Aging\u2013Alzheimer\u2019s Association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease: A practical approach","volume":"123","author":"Montine","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0306-4522(02)00942-9","article-title":"Stereologic analysis of neu-rofibrillary tangle formation in prefrontal cortex area 9 in aging and Alzheimer\u2019s disease","volume":"117","author":"Gold","year":"2003","journal-title":"Neuroscience"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1126\/science.3544219","article-title":"Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer\u2019s disease","volume":"235","author":"Selkoe","year":"1987","journal-title":"Science"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.gene.2004.07.013","article-title":"Tau gene (MAPT) sequence variation among primates","volume":"341","author":"Holzer","year":"2004","journal-title":"Gene"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0304-3940(94)90270-4","article-title":"Neurofibrillary tangles in the cerebral cortex of sheep","volume":"170","author":"Nelson","year":"1994","journal-title":"Neurosci. Lett."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/0169-328X(91)90088-F","article-title":"Conservation of the sequence of the Alzheimer\u2019s disease amyloid peptide in dog, polar bear and five other mammals by cross-species polymerase chain reaction analysis","volume":"10","author":"Johnstone","year":"1991","journal-title":"Mol. Brain Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.conb.2015.10.004","article-title":"Microglial genes regulating neuroinflammation in the progression of Alzheimer\u2019s disease","volume":"36","author":"Phillips","year":"2016","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_130","first-page":"59","article-title":"Inflammatory process in Alzheimer\u2019s Disease","volume":"7","author":"Rios","year":"2013","journal-title":"Front. Integr. Neurosci."},{"key":"ref_131","first-page":"a006346","article-title":"Inflammation in Alzheimer Disease\u2014A Brief Review of the Basic Science and Clinical Literature","volume":"2","author":"Rogers","year":"2011","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.neurobiolaging.2014.07.024","article-title":"Activated human microglia stimulate neuroblastoma cells to upregulate production of beta amyloid protein and tau: Implications for Alzheimer\u2019s disease pathogenesis","volume":"36","author":"Lee","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0140-6736(01)05625-2","article-title":"In-vivo measurement of activated microglia in dementia","volume":"358","author":"Cagnin","year":"2001","journal-title":"Lancet"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"8354","DOI":"10.1523\/JNEUROSCI.0616-08.2008","article-title":"Microglial Dysfunction and Defective \u03b2-Amyloid Clearance Pathways in Aging Alzheimer\u2019s Disease Mice","volume":"28","author":"Hickman","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2174\/156720509787602906","article-title":"Visualization of brain amyloid and microglial activation in mouse models of Alzheimer\u2019s disease","volume":"6","author":"Higuchi","year":"2009","journal-title":"Curr. Alzheimer Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"6333","DOI":"10.1523\/JNEUROSCI.0829-08.2008","article-title":"Complement C3 Deficiency Leads to Accelerated Amyloid Plaque Deposition and Neurodegeneration and Modulation of the Microglia\/Macrophage Phenotype in Amyloid Precursor Protein Transgenic Mice","volume":"28","author":"Maier","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1093\/brain\/awv081","article-title":"Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain","volume":"138","author":"Maphis","year":"2015","journal-title":"Brain"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/693851","article-title":"Proliferation in the Alzheimer Hippocampus Is due to Microglia, Not Astroglia, and Occurs at Sites of Amyloid Deposition","volume":"2014","author":"Marlatt","year":"2014","journal-title":"Neural Plast."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1002\/cne.24484","article-title":"Microglia changes associated to Alzheimer\u2019s disease pathology in aged chimpanzees","volume":"526","author":"Edler","year":"2018","journal-title":"J. Comp. Neurol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/cne.21744","article-title":"Tauopathy with paired helical filaments in an aged chim-panzee","volume":"509","author":"Rosen","year":"2008","journal-title":"J. Comp. Neurol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"9382","DOI":"10.1073\/pnas.91.20.9382","article-title":"Neuropathology and apolipoprotein E profile of aged chimpanzees: Implications for Alzheimer disease","volume":"91","author":"Gearing","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/S0197-4580(96)00164-9","article-title":"A\u03b240 is a major form of \u03b2-amyloid in nonhuman primates","volume":"17","author":"Gearing","year":"1996","journal-title":"Neurobiol. Aging"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"4318","DOI":"10.1002\/cne.23428","article-title":"Alzheimer\u2019s disease pathology in the neocortex and hippocampus of the western lowland gorilla (Gorilla gorilla gorilla)","volume":"521","author":"Perez","year":"2013","journal-title":"J. Comp. Neurol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.neurobiolaging.2015.12.017","article-title":"Early Alzheimer\u2019s disease\u2013type pathology in the frontal cortex of wild mountain gorillas (Gorilla beringei beringei)","volume":"39","author":"Perez","year":"2016","journal-title":"Neurobiol. Aging"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1538\/expanim.50.77","article-title":"Senile Plaques in an Aged Western Lowland Gorilla","volume":"50","author":"Kimura","year":"2001","journal-title":"Exp. Anim."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0197-4580(97)00012-2","article-title":"Beta-amyloid (A-beta) deposition in the brains of aged orangutans","volume":"18","author":"Gearing","year":"1997","journal-title":"Neurobiol. Aging"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/jnen\/59.1.39","article-title":"Filamentous Tau Pathology in Nerve Cells, Astrocytes, and Oligodendrocytes of Aged Baboons","volume":"59","author":"Schultz","year":"2000","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/j.1365-2990.2011.01246.x","article-title":"Cerebral amyloid \u03b2(42) deposits and microvascular pathology in ageing baboons","volume":"38","author":"Wegner","year":"2012","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s004010000183","article-title":"Abnormally phosphorylated protein tau in the cortex of aged individuals of various mammalian orders","volume":"100","author":"Klein","year":"2000","journal-title":"Acta Neuropathol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"26239","DOI":"10.1073\/pnas.1902301116","article-title":"Oligomeric A\u03b2 in the monkey brain impacts synaptic integrity and induces accelerated cortical aging","volume":"116","author":"Beckman","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Beckman, D., Chakrabarty, P., Ott, S., Dao, A., Zhou, E., Janssen, W.G., Donis-Cox, K., Muller, S., Kordower, J.H., and Morrison, J.H. (2021). A novel tau-based rhesus monkey model of Alzheimer\u2019s pathogenesis. Alzheimers Dement.","DOI":"10.1002\/alz.12318"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"26230","DOI":"10.1073\/pnas.1903671116","article-title":"Alzheimer\u2019s-like pathology in aging rhesus macaques: Unique opportunity to study the etiology and treatment of Alzheimer\u2019s disease","volume":"116","author":"Arnsten","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/j.1749-6632.1993.tb23058.x","article-title":"The Age of Biosenescence and the Incidence of Cerebral \u03b2-Amyloidosis in Aged Captive Rhesus Monkeysa","volume":"695","author":"Uno","year":"1993","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.jalz.2017.11.005","article-title":"The aged rhesus macaque manifests Braak stage III\/IV Alzheimer\u2019s-like pathology","volume":"14","author":"Paspalas","year":"2017","journal-title":"Alzheimers Dement."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e12978","DOI":"10.1111\/acel.12978","article-title":"Brains of rhesus monkeys display A\u03b2 deposits and glial pathology while lacking A\u03b2 dimers and other Alzheimer\u2019s pathologies","volume":"18","author":"Zhang","year":"2019","journal-title":"Aging Cell"},{"key":"ref_156","first-page":"1423","article-title":"Homology of the amyloid beta protein precursor in monkey and human supports a primate model for beta amyloidosis in Alzheimer\u2019s disease","volume":"138","author":"Podlisny","year":"1991","journal-title":"Am. J. Pathol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.bbrc.2003.09.012","article-title":"Age-related changes of Alzheimer\u2019s disease-associated proteins in cynomolgus monkey brains","volume":"310","author":"Kimura","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_158","first-page":"173","article-title":"Poor memory performance in aged cynomolgus monkeys with hippocampal atrophy, depletion of amyloid beta 1-42 and accumulation of tau proteins in cerebrospinal fluid","volume":"28","author":"Darusman","year":"2014","journal-title":"Vivo"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.brainres.2009.12.005","article-title":"Alzheimer-type tau pathology in advanced aged nonhuman primate brains harboring substantial amyloid deposition","volume":"1315","author":"Oikawa","year":"2010","journal-title":"Brain Res."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1007\/s004010000215","article-title":"Abnormal neuronal and glial argyrophilic fibrillary structures in the brain of an aged albino cynomolgus monkey (Macaca fascicularis)","volume":"100","author":"Kiatipattanasakul","year":"2000","journal-title":"Acta Neuropathol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/j.1600-0684.1998.tb00244.x","article-title":"Histopathological studies of senile plaques and cerebral amyloidosis in cynomolgus monkeys","volume":"27","author":"Nakamura","year":"1998","journal-title":"J. Med. Primatol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.neurobiolaging.2017.12.011","article-title":"Aging African green monkeys manifest transcriptional, pathological, and cognitive hallmarks of human Alzheimer\u2019s disease","volume":"64","author":"Cramer","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/j.neurobiolaging.2013.03.023","article-title":"Development of amyloid burden in African Green monkeys","volume":"34","author":"Kalinin","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0002-9440(10)63296-8","article-title":"Alzheimer\u2019s disease abeta vaccine reduces central nervous system abeta levels in a non-human primate, the Caribbean vervet","volume":"165","author":"Lemere","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_165","first-page":"155","article-title":"Cerebral beta-amyloid angiopathy in aged squirrel monkeys","volume":"22","author":"Elfenbein","year":"2007","journal-title":"Histol. Histopathol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0006-8993(97)00624-0","article-title":"Characterization of amyloid \u03b2 protein species in cerebral amyloid angiopathy of a squirrel monkey by immunocytochemistry and enzyme-linked immunosorbent assay","volume":"764","author":"Sawamura","year":"1997","journal-title":"Brain Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/BF00307691","article-title":"Amyloid in the brains of aged squirrel monkeys","volume":"80","author":"Walker","year":"1990","journal-title":"Acta Neuropathol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"519","DOI":"10.3233\/JAD-160981","article-title":"Amyloid-Related Imaging Abnormalities in an Aged Squirrel Monkey with Cerebral Amyloid Angiopathy","volume":"57","author":"Heuer","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1089\/rej.2008.0677","article-title":"Cerebral Amyloid-Beta Protein Accumulation with Aging in Cotton-Top Tamarins: A Model of Early Alzheimer\u2019s Disease?","volume":"11","author":"Lemere","year":"2008","journal-title":"Rejuvenation Res."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s004010100429","article-title":"Amyloid-beta deposits in the cerebral cortex of the aged common marmoset (callithrix jac-chus): Incidence and chemical composition","volume":"103","author":"Geula","year":"2002","journal-title":"Acta Neuropathol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1354\/vp.43-5-777","article-title":"Natural Occurrence of Amyloid-A\u03b2 Deposits in the Brain of Young Common Marmosets (Callithrix jacchus): A Morphological and Immunohistochemical Evaluation","volume":"43","author":"Palazzi","year":"2006","journal-title":"Vet. Pathol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1007\/s00702-005-0385-2","article-title":"Very long term studies of the seeding of \u03b2-amyloidosis in primates","volume":"113","author":"Ridley","year":"2005","journal-title":"J. Neural Transm."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"11433","DOI":"10.1074\/jbc.RA119.008415","article-title":"Tau isoform expression and phosphorylation in marmoset brains","volume":"294","author":"Sharma","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3233\/JAD-160673","article-title":"Acceleration of Amyloidosis by Inflammation in the Amyloid-Beta Marmoset Monkey Model of Alzheimer\u2019s Disease","volume":"55","author":"Philippens","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s004010050684","article-title":"Quantitative analysis of tau protein-immunoreactive accumulations and \u03b2 amyloid protein deposits in the cerebral cortex of the mouse lemur, Microcebus murinus","volume":"94","author":"Giannakopoulos","year":"1997","journal-title":"Acta Neuropathol."},{"key":"ref_176","first-page":"169","article-title":"B-amyloid protein precursor in Microcebus murinus: Genotyping and brain localization","volume":"3","author":"Silhol","year":"1996","journal-title":"Neurobiol. Aging"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/nbdi.1999.0270","article-title":"Immunohistochemical Analysis of Cerebral Cortical and Vascular Lesions in the Primate Microcebus murinus Reveal Distinct Amyloid \u03b21\u201342 and \u03b21\u201340 Immunoreactivity Profiles","volume":"7","author":"Keller","year":"2000","journal-title":"Neurobiol. Dis."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0197-4580(94)90115-5","article-title":"Identification of amyloid beta protein in the brain of the small, short-lived Lemurian primate Microcebus murinus","volume":"15","author":"Bons","year":"1994","journal-title":"Neurobiol. Aging"},{"key":"ref_179","first-page":"85","article-title":"Biochemical characterization of Tau proteins during cerebral aging of the lemurian primate Microcebus murinus","volume":"318","author":"Delacourte","year":"1995","journal-title":"C. R. Acad. Sci. Ser. III Sci. Vie"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/914947","article-title":"Cognitive Deterioration and Associated Pathology Induced by Chronic Low-Level Aluminum Ingestion in a Translational Rat Model Provides an Explanation of Alzheimer\u2019s Disease, Tests for Susceptibility and Avenues for Treatment","volume":"2012","author":"Walton","year":"2012","journal-title":"Int. J. Alzheimers Dis."},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Onos, K.D., Uyar, A., Keezer, K.J., Jackson, H.M., Preuss, C., Acklin, C.J., O\u2019Rourke, R., Buchanan, R., Cossette, T.L., and Rizzo, S.J.S. (2019). Enhancing face validity of mouse models of Alzheimer\u2019s disease with natural genetic variation. PLoS Genet., 15.","DOI":"10.1371\/journal.pgen.1008155"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s00401-016-1662-x","article-title":"Alzheimer\u2019s disease: Experimental models and reality","volume":"133","author":"Drummond","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0014-5793(93)81399-K","article-title":"Amyloidogenicity of rodent and human beta A4 sequences","volume":"324","author":"Dyrks","year":"1993","journal-title":"FEBS Lett."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0165-3806(03)00056-7","article-title":"Isoforms changes of tau protein during development in various species","volume":"142","author":"Takuma","year":"2003","journal-title":"Dev. Brain Res."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/j.neurobiolaging.2013.11.020","article-title":"Aging, cortical injury and Alzheimer\u2019s disease-like pathology in the guinea pig brain","volume":"35","author":"Bates","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0006-8993(94)01160-J","article-title":"Ultrastructural localization of amyloid protein precursor in the normal and postischemic gerbil brain","volume":"672","author":"Tomimoto","year":"1995","journal-title":"Brain Res."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/0304-3940(92)90061-B","article-title":"Regional accumulation of amyloid \u03b2A4 protein precursor in the gerbil brain following transient cerebral ischemia","volume":"146","author":"Wakita","year":"1992","journal-title":"Neurosci. Lett."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.3233\/JAD-170594","article-title":"Does the Genetic Feature of the Chinese Tree Shrew (Tupaia belangeri chinensis) Support Its Potential as a Viable Model for Alzheimer\u2019s Disease Research?","volume":"61","author":"Fan","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1177\/0300985815623997","article-title":"Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases","volume":"53","author":"Youssef","year":"2016","journal-title":"Vet. Pathol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.neurobiolaging.2006.09.018","article-title":"Region specific neuron loss in the aged canine hippocampus is reduced by enrichment","volume":"29","author":"Head","year":"2008","journal-title":"Neurobiol. Aging"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0304-3940(94)90589-4","article-title":"Abnormally phosphorylated tau protein related to the formation of neurofibrillary tangles and neuropil threads in the cerebral cortex of sheep and goat","volume":"171","author":"Braak","year":"1994","journal-title":"Neurosci. Lett."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jcpa.2010.11.004","article-title":"Histopathological and Immunohistochemical Comparison of the Brain of Human Patients with Alzheimer\u2019s Disease and the Brain of Aged Dogs with Cognitive Dysfunction","volume":"145","author":"Yu","year":"2011","journal-title":"J. Comp. Pathol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"604","DOI":"10.3389\/fnins.2019.00604","article-title":"Canine Cognitive Dysfunction and Alzheimer\u2019s Disease\u2014Two Facets of the Same Disease?","volume":"13","author":"Mihevc","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3389\/fnagi.2018.00007","article-title":"An Aged Canid with Behavioral Deficits Exhibits Blood and Cerebrospinal Fluid Amyloid Beta Oligomers","volume":"10","author":"Rusbridge","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s004010050714","article-title":"Deposition of amyloid \u03b2 protein (A\u03b2) subtypes [A\u03b240 and A\u03b242(43)] in canine senile plaques and cerebral amyoloid angiopathy","volume":"94","author":"Nakamura","year":"1997","journal-title":"Acta Neuropathol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/j.1748-5827.2007.00386.x","article-title":"Cognitive dysfunction and the neurobiology of ageing in cats","volume":"48","author":"Moffat","year":"2007","journal-title":"J. Small Anim. Pract."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.neurobiolaging.2004.06.015","article-title":"\u03b2-Amyloid deposition and tau phosphorylation in clinically characterized aged cats","volume":"26","author":"Head","year":"2005","journal-title":"Neurobiol. Aging"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s40478-015-0258-3","article-title":"The domestic cat as a natural animal model of Alzheimer\u2019s disease","volume":"3","author":"Chambers","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1177\/0300985811410719","article-title":"Beta Amyloid Deposition and Neurofibrillary Tangles Spontaneously Occur in the Brains of Captive Cheetahs (Acinonyx jubatus)","volume":"49","author":"Serizawa","year":"2011","journal-title":"Vet. Pathol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/0197-4580(95)02062-4","article-title":"Carboxy terminal of \u03b2-amyloid deposits in aged human, canine, and polar bear brains","volume":"17","author":"Tekirian","year":"1996","journal-title":"Neurobiol. Aging"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1097\/00005072-198811000-00006","article-title":"Neurofibrillary Tangles and Senile Plaques in Aged Bears","volume":"47","author":"Cork","year":"1988","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1177\/030098589503200410","article-title":"Senile Plaques and Other Senile Changes in the Brain of an Aged American Black Bear","volume":"32","author":"Uchida","year":"1995","journal-title":"Vet. Pathol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0197-4580(95)02069-1","article-title":"A\u03b2-Associated cerebral angiopathy and senile plaques with neurofibrillary tangles and cerebral hemorrhage in an aged wolverine (Gulo gulo)","volume":"17","author":"Roertgen","year":"1996","journal-title":"Neurobiol. Aging"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40478-020-01104-3","article-title":"Amyloid \u03b2 and tau pathology in brains of aged pinniped species (sea lion, seal, and walrus)","volume":"9","author":"Takaichi","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_205","doi-asserted-by":"crossref","unstructured":"Sacchini, S., D\u00edaz-Delgado, J., de Los Monteros, A.E., Paz, Y., de Quir\u00f3s, Y.B., Sierra, E., Arbelo, M., Herr\u00e1ez, P., and Fern\u00e1ndez, A. (2020). Amyloid-beta peptide and phosphorylated tau in the frontopolar cerebral cortex and in the cerebellum of toothed whales: Aging versus hypoxia. Biol. Open, 9.","DOI":"10.1242\/bio.054734"},{"key":"ref_206","first-page":"195","article-title":"Alzheimer\u2019s disease in humans and other animals: A consequence of postreproductive life span and longevity rather than aging","volume":"14","author":"Iradi","year":"2017","journal-title":"Alzheimers Dement."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"e000700","DOI":"10.1136\/vetreccr-2018-000700","article-title":"Alzheimer\u2019s disease-like pathological lesions in an aged bottlenose dolphin (Tursiops truncatus)","volume":"7","author":"Stylianaki","year":"2019","journal-title":"Vet. Rec. Case Rep."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Davis, D.A., Mondo, K., Stern, E., Annor, A.K., Murch, S.J., Coyne, T.M., Brand, L.E., Niemeyer, M.E., Sharp, S., and Bradley, W.G. (2019). Cyanobacterial neurotoxin BMAA and brain pathology in stranded dolphins. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0213346"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.neurobiolaging.2017.06.020","article-title":"Alzheimer\u2019s disease markers in the aged sheep (Ovis aries)","volume":"58","author":"Reid","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"875","DOI":"10.3233\/JAD-151007","article-title":"Characterization of Amyloid-\u03b2 Deposits in Bovine Brains","volume":"51","author":"Costassa","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0197-4580(00)00179-2","article-title":"Hyperphosphorylated protein tau is restricted to neurons devoid of perineuronal nets in the cortex of aged bison","volume":"22","year":"2001","journal-title":"Neurobiol. Aging"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/BF02899034","article-title":"Role of microglia in plaque formation in senile dementia of the Alzheimer type","volume":"51","author":"Rozemuller","year":"1986","journal-title":"Virchows Arch. B Cell Pathol. Incl. Mol. Pathol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.biopsych.2014.05.021","article-title":"Stage-Specific Changes in Neurogenic and Glial Markers in Alzheimer\u2019s Disease","volume":"77","author":"Ekonomou","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s11481-009-9163-5","article-title":"Life and Death of Microglia","volume":"4","author":"Streit","year":"2009","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/jemt.1120","article-title":"Microglia in neurodegeneration: Molecular aspects","volume":"54","year":"2001","journal-title":"Microsc. Res. Tech."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1159\/000322228","article-title":"Presence of Reactive Microglia and Neuroinflammatory Mediators in a Case of Frontotemporal Dementia with P301S Mutation","volume":"8","author":"Bellucci","year":"2011","journal-title":"Neurodegener. Dis."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.ajpath.2011.05.047","article-title":"Reactive Glia not only Associates with Plaques but also Parallels Tangles in Alzheimer\u2019s Disease","volume":"179","author":"Mielke","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/bpa.12902","article-title":"Accumulation of neurofibrillary tangles and activated microglia is associated with lower neuron densities in the aphasic variant of Alzheimer\u2019s disease","volume":"31","author":"Ohm","year":"2021","journal-title":"Brain Pathol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"325","DOI":"10.2353\/ajpath.2010.090937","article-title":"Neuronal and axonal loss are selectively linked to fibrillar amyloid-beta within plaques of the aged primate cerebral cortex","volume":"177","author":"Shah","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/nm0798-827","article-title":"Aging renders the brain vulnerable to amyloid beta-protein neurotoxicity","volume":"4","author":"Geula","year":"1998","journal-title":"Nat. Med."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.neurobiolaging.2009.02.025","article-title":"Microglia activation mediates fibrillar amyloid-\u03b2 toxicity in the aged primate cortex","volume":"32","author":"Leung","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"13629","DOI":"10.1523\/JNEUROSCI.1353-14.2014","article-title":"Alzheimer\u2019s Disease-Like Pathology Induced by Amyloid-\u03b2 Oligomers in Nonhuman Primates","volume":"34","author":"Silva","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_224","first-page":"307","article-title":"Microglial response to amyloid plaques in APPsw transgenic mice","volume":"152","author":"Frautschy","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1038\/cddis.2009.2","article-title":"Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer\u2019s disease","volume":"1","author":"Witton","year":"2010","journal-title":"Cell Death Dis."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.neulet.2013.06.036","article-title":"Increased densities of resting and activated microglia in the dentate gyrus follow senile plaque formation in the CA1 subfield of the hippocampus in the triple transgenic model of Alzheimer\u2019s disease","volume":"552","author":"Noristani","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1742-2094-2-23","article-title":"Early correlation of microglial activation with enhanced tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer\u2019s disease mice","volume":"2","author":"Janelsins","year":"2005","journal-title":"J. Neuroinflamm."},{"key":"ref_228","first-page":"83","article-title":"The pathology of APP transgenic mice: A model of Alzheimer\u2019s disease or simply overexpression of APP?","volume":"24","author":"Howlett","year":"2009","journal-title":"Histol. Histopathol."},{"key":"ref_229","first-page":"720","article-title":"Rapid appearance and local toxicity of amyloid-\u03b2 plaques in a mouse model of Alzheimer\u2019s disease","volume":"451","author":"Prada","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0002-9440(10)62993-8","article-title":"Cerebral microvascular amyloid beta protein dep-osition induces vascular degeneration and neuroinflammation in transgenic mice expressing human vasculotropic mutant amyloid beta precursor protein","volume":"167","author":"Miao","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1016\/S0002-9440(10)65423-5","article-title":"Association of Microglia with Amyloid Plaques in Brains of APP23 Transgenic Mice","volume":"154","author":"Stalder","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.neurobiolaging.2017.03.021","article-title":"Immune hyperreactivity of amyloid-beta plaque-associated microglia in Alzheimer\u2019s disease","volume":"55","author":"Yin","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.neurobiolaging.2003.08.008","article-title":"Inflammation occurs early during the A\u03b2 deposition process in TgCRND8 mice","volume":"25","author":"Dudal","year":"2004","journal-title":"Neurobiol. Aging"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"8843","DOI":"10.1523\/JNEUROSCI.2868-05.2005","article-title":"Lipopolysaccharide-Induced Inflammation Exacerbates Tau Pathology by a Cyclin-Dependent Kinase 5-Mediated Pathway in a Transgenic Model of Alzheimer\u2019s Disease","volume":"25","author":"Kitazawa","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Wright, A.L., Zinn, R., Hohensinn, B., Konen, L.M., Beynon, S.B., Tan, R.P., Clark, I.A., Abdipranoto, A., and Vissel, B. (2013). Neuroinflammation and Neuronal Loss Precede A\u03b2 Plaque Deposition in the hAPP-J20 Mouse Model of Alzheimer\u2019s Disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059586"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1038\/nn.2432","article-title":"Formation and maintenance of Alzheimer\u2019s disease \u03b2-amyloid plaques in the absence of microglia","volume":"12","author":"Grathwohl","year":"2009","journal-title":"Nat. Neurosci."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"11650","DOI":"10.1523\/JNEUROSCI.3024-08.2008","article-title":"Inflammatory Response in the Hippocampus of PS1M146L\/APP751SL Mouse Model of Alzheimer\u2019s Disease: Age-Dependent Switch in the Microglial Phenotype from Alternative to Classic","volume":"28","author":"Jimenez","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13024-017-0188-6","article-title":"Microglia limit the expansion of \u03b2-amyloid plaques in a mouse model of Alzheimer\u2019s disease","volume":"12","author":"Zhao","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1093\/brain\/aww016","article-title":"Eliminating microglia in Alzheimer\u2019s mice prevents neuronal loss without modulating amyloid-\u03b2 pathology","volume":"139","author":"Spangenberg","year":"2016","journal-title":"Brain"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.neuron.2010.08.023","article-title":"Regulation of Tau Pathology by the Microglial Fractalkine Receptor","volume":"68","author":"Bhaskar","year":"2010","journal-title":"Neuron"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.neuron.2007.01.010","article-title":"Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model","volume":"53","author":"Yoshiyama","year":"2007","journal-title":"Neuron"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-021-02124-z","article-title":"Uncovering sex differences of rodent microglia","volume":"18","author":"Han","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1097\/NEN.0000000000000230","article-title":"Detection and Quantification of \u03b2-Amyloid, Pyroglutamyl A\u03b2, and Tau in Aged Canines","volume":"74","author":"Schmidt","year":"2015","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1292\/jvms.55.637","article-title":"Double-Labeling Immunohistochemical Studies on Canine Senile Plaques and Cerebral Amyloid Angiopathy","volume":"55","author":"Uchida","year":"1993","journal-title":"J. Vet. Med. Sci."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3109\/13506120309041730","article-title":"Canine counterpart of senile dementia of the Alzheimer type: Amyloid plaques near capillaries but lack of spatial relationship with activated microglia and macrophages","volume":"10","author":"Rofina","year":"2003","journal-title":"Amyloid"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s00401-006-0052-1","article-title":"Canine cognitive deficit correlates with diffuse plaque maturation and S100\u03b2 (\u2212) astrocytosis but not with insulin cerebrospinal fluid level","volume":"111","author":"Pugliese","year":"2006","journal-title":"Acta Neuropathol."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/BF00294609","article-title":"Microglia in cerebellar plaques in Alzheimer\u2019s disease","volume":"80","author":"Mattiace","year":"1990","journal-title":"Acta Neuropathol."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1002\/jnr.490330407","article-title":"MHC class II-positive microglia in human brain: Association with Alzheimer lesions","volume":"33","author":"Perlmutter","year":"1992","journal-title":"J. Neurosci. Res."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1212\/WNL.38.8.1285","article-title":"Reactive microglia are positive for HLA-DR in the substantia nigra of Par-kinson\u2019s and Alzheimer\u2019s disease brains","volume":"38","author":"McGeer","year":"1988","journal-title":"Neurology"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/0165-5728(89)90115-X","article-title":"Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease","volume":"24","author":"Itagaki","year":"1989","journal-title":"J. Neuroimmunol."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1097\/00005072-199311000-00007","article-title":"Morphometric analysis of microglia in Alzheimer\u2019s disease","volume":"52","author":"Carpenter","year":"1993","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.neuron.2013.04.014","article-title":"Alzheimer\u2019s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta","volume":"78","author":"Griciuc","year":"2013","journal-title":"Neuron"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.2174\/138161212799315885","article-title":"Nonhuman Primate Models of Alzheimer-Like Cerebral Proteopathy","volume":"18","author":"Heuer","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1523\/JNEUROSCI.21-04-01179.2001","article-title":"\u03b2-Amyloid Stimulation of Microglia and Monocytes Results in TNF\u03b1-Dependent Expression of Inducible Nitric Oxide Synthase and Neuronal Apoptosis","volume":"21","author":"Combs","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"247","DOI":"10.2174\/1568010053586237","article-title":"Mechanisms of Cell Signaling and Inflammation in Alzheimers Disease","volume":"4","author":"Ho","year":"2005","journal-title":"Curr. Drug Target Inflamm. Allergy"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1189\/jlb.0705377","article-title":"Gene expression changes by amyloid \u03b2 peptide-stimulated human postmortem brain microglia identify activation of multiple inflammatory processes","volume":"79","author":"Walker","year":"2005","journal-title":"J. Leukoc. Biol."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/S0197-4580(01)00311-6","article-title":"Modeling microglial activation in Alzheimer\u2019s disease with human postmortem microglial cultures","volume":"22","author":"Lue","year":"2001","journal-title":"Neurobiol. Aging"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-019-1399-2","article-title":"Glial activation and inflammation along the Alzheimer\u2019s disease continuum","volume":"16","author":"Nordengen","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-30487-6","article-title":"IL-1\u03b2, IL-6, TNF- \u03b1 and CRP in Elderly Patients with Depression or Alzheimer\u2019s disease: Systematic Review and Meta-Analysis","volume":"8","author":"Ng","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"16622","DOI":"10.1038\/srep16622","article-title":"Identification of neurotoxic cytokines by profiling Alzheimer\u2019s disease tissues and neuron culture viability screening","volume":"5","author":"Wood","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/j.1750-3639.2008.00188.x","article-title":"Monocyte Chemoattractant Protein-1 Plays a Dominant Role in the Chronic Inflammation Observed in Alzheimer\u2019s Disease","volume":"19","author":"Sokolova","year":"2009","journal-title":"Brain Pathol."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.nbd.2018.10.009","article-title":"Distinct cytokine profiles in human brains resilient to Alzheimer\u2019s pathology","volume":"121","author":"Weinstock","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1523\/JNEUROSCI.3268-10.2011","article-title":"CD45 Deficiency Drives Amyloid- Peptide Oligomers and Neuronal Loss in Alzheimer\u2019s Disease Mice","volume":"31","author":"Zhu","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1742-2094-5-23","article-title":"Toll-like receptor 4-dependent upregulation of cytokines in a transgenic mouse model of Alzheimer\u2019s disease","volume":"5","author":"Jin","year":"2008","journal-title":"J. Neuroinflamm."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S0197-4580(99)00065-2","article-title":"Evidence for glial-mediated inflammation in aged APPSW transgenic mice","volume":"20","author":"Benzing","year":"1999","journal-title":"Neurobiol. Aging"},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S0165-5728(02)00050-4","article-title":"Up-regulation of the inflammatory cytokines IFN-\u03b3 and IL-12 and down-regulation of IL-4 in cerebral cortex regions of APPSWE transgenic mice","volume":"126","author":"Abbas","year":"2002","journal-title":"J. Neuroimmunol."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"680","DOI":"10.2353\/ajpath.2007.060378","article-title":"Interferon-\u03b3 and Tumor Necrosis Factor-\u03b1 Regulate Amyloid-\u03b2 Plaque Deposition and \u03b2-Secretase Expression in Swedish Mutant APP Transgenic Mice","volume":"170","author":"Yamamoto","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"870","DOI":"10.2174\/1567205014666170317113606","article-title":"Impact of Cytokines and Chemokines on Alzheimer\u2019s Disease Neuropathological Hallmarks","volume":"14","author":"Domingues","year":"2017","journal-title":"Curr. Alzheimer Res."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1006\/exnr.2000.7393","article-title":"Interleukin-1 Promotes Expression and Phosphorylation of Neurofilament and tau Proteins in Vivo","volume":"163","author":"Shengab","year":"2000","journal-title":"Exp. Neurol."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.2353\/ajpath.2009.090059","article-title":"Interferon-\u03b3 Differentially Affects Alzheimer\u2019s Disease Pathologies and Induces Neurogenesis in Triple Transgenic-AD Mice","volume":"175","author":"Mastrangelo","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"4384","DOI":"10.1096\/fj.15-275834","article-title":"IFN-\u03b3 promotes \u03c4 phosphorylation without affecting mature tangles","volume":"29","author":"Li","year":"2015","journal-title":"FASEB J."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.brainres.2010.10.053","article-title":"Anti-TNF-\u03b1 reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP\/PS1 transgenic mouse brains","volume":"1368","author":"Shi","year":"2011","journal-title":"Brain Res."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/1742-2094-9-106","article-title":"Tumor necrosis factor-\u03b1 synthesis inhibitor 3,6\u2032-dithiothalidomide attenuates markers of inflammation, Alzheimer pathology and behavioral deficits in animal models of neuroinflammation and Alzheimer\u2019s disease","volume":"9","author":"Tweedie","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_274","doi-asserted-by":"crossref","unstructured":"Simpson, D.S.A., and Oliver, P.L. (2020). ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease. Antioxidants, 9.","DOI":"10.3390\/antiox9080743"},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.3233\/JAD-170543","article-title":"Oxidative Stress, Amyloid-\u03b2 Peptide, and Altered Key Molecular Pathways in the Pathogenesis and Progression of Alzheimer\u2019s Disease","volume":"62","author":"Butterfield","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1523\/JNEUROSCI.18-06-02161.1998","article-title":"Fibrillar \u03b2-Amyloid Induces Microglial Phagocytosis, Expression of Inducible Nitric Oxide Synthase, and Loss of a Select Population of Neurons in the Rat CNSIn Vivo","volume":"18","author":"Weldon","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1002\/glia.22966","article-title":"Dark microglia: A new phenotype predominantly associated with pathological states","volume":"64","author":"Bisht","year":"2016","journal-title":"Glia"},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"583","DOI":"10.15252\/embj.201694591","article-title":"Young microglia restore amyloid plaque clearance of aged microglia","volume":"36","author":"Daria","year":"2017","journal-title":"EMBO J."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1093\/brain\/awn331","article-title":"Powerful beneficial effects of macrophage colony-stimulating factor on -amyloid deposition and cognitive impairment in Alzheimer\u2019s disease","volume":"132","author":"Boissonneault","year":"2008","journal-title":"Brain"},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1097\/NEN.0b013e31818b48db","article-title":"Nonviral DNA Vaccination Augments Microglial Phagocytosis of \u03b2-Amyloid Deposits as a Major Clearance Pathway in an Alzheimer Disease Mouse Model","volume":"67","author":"Okura","year":"2008","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1002\/glia.23074","article-title":"Microglia contributes to plaque growth by cell death due to uptake of amyloid \u03b2 in the brain of Alzheimer\u2019s disease mouse model","volume":"64","author":"Baik","year":"2016","journal-title":"Glia"},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"11161","DOI":"10.1038\/srep11161","article-title":"Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody","volume":"5","author":"Luo","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"8240","DOI":"10.1523\/JNEUROSCI.1808-05.2005","article-title":"Microglial Phagocytosis Induced by Fibrillar -Amyloid and IgGs Are Differentially Regulated by Proinflammatory Cytokines","volume":"25","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3389\/fncel.2019.00457","article-title":"Distinct Signaling Pathways Regulate TREM2 Phagocytic and NF\u03baB Antagonistic Activities","volume":"13","author":"Yao","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"279","DOI":"10.3233\/JAD-2011-101014","article-title":"Microglia Demonstrate Age-Dependent Interaction with Amyloid-\u03b2 Fibrils","volume":"25","author":"Floden","year":"2011","journal-title":"J. Alzheimers Dis."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40035-017-0072-x","article-title":"The role of exosomes in the pathogenesis of Alzheimer\u2019 disease","volume":"6","author":"Xiao","year":"2017","journal-title":"Transl. Neurodegener."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/nrn.2015.29","article-title":"Extracellular vesicles round off communication in the nervous system","volume":"17","author":"Budnik","year":"2016","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"11172","DOI":"10.1073\/pnas.0603838103","article-title":"Alzheimer\u2019s disease beta-amyloid peptides are released in association with exosomes","volume":"103","author":"Rajendran","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1750-1326-7-42","article-title":"Exosomal cell-to-cell transmission of alpha synuclein oligomers","volume":"7","author":"Danzer","year":"2012","journal-title":"Mol. Neurodegener."},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1016\/S0002-9440(10)64463-X","article-title":"Intraneuronal Alzheimer A\u03b242 Accumulates in Multivesicular Bodies and Is Associated with Synaptic Pathology","volume":"161","author":"Takahashi","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13195-020-00623-4","article-title":"Alzheimer\u2019s disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles","volume":"12","author":"Guo","year":"2020","journal-title":"Alzheimers Res. Ther."},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"43108","DOI":"10.1074\/jbc.M112.404467","article-title":"The Exosome Secretory Pathway Transports Amyloid Precursor Protein Carboxyl-terminal Fragments from the Cell into the Brain Extracellular Space","volume":"287","author":"Gauthier","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00401-018-1868-1","article-title":"Alzheimer\u2019s disease pathology propagation by exosomes containing toxic amyloid-beta oligomers","volume":"136","author":"Sinha","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/cdd.2013.180","article-title":"Microglia convert aggregated amyloid-\u03b2 into neurotoxic forms through the shedding of microvesicles","volume":"21","author":"Joshi","year":"2014","journal-title":"Cell Death Differ."},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1016\/j.neurobiolaging.2014.02.012","article-title":"Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer\u2019s disease","volume":"35","author":"Dinkins","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"12445","DOI":"10.1074\/jbc.M115.709485","article-title":"Extracellular Vesicles Isolated from the Brains of rTg4510 Mice Seed Tau Protein Aggregation in a Threshold-dependent Manner","volume":"291","author":"Polanco","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/nn.4132","article-title":"Depletion of microglia and inhibition of exosome synthesis halt tau propagation","volume":"18","author":"Asai","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13024-020-00396-2","article-title":"P2RX7 inhibitor suppresses exosome secretion and disease phenotype in P301S tau transgenic mice","volume":"15","author":"Ruan","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-45676-0","article-title":"BIN1 favors the spreading of Tau via extracellular vesicles","volume":"9","author":"Crotti","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"24488","DOI":"10.1074\/jbc.M114.577213","article-title":"Decreased Amyloid-\u03b2 Pathologies by Intracerebral Loading of Glycosphingolipid-enriched Exosomes in Alzheimer Model Mice","volume":"289","author":"Yuyama","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.febslet.2014.11.027","article-title":"A potential function for neuronal exosomes: Sequestering intracerebral amyloid-\u03b2 peptide","volume":"589","author":"Yuyama","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"10977","DOI":"10.1074\/jbc.M111.324616","article-title":"Sphingolipid-modulated Exosome Secretion Promotes Clearance of Amyloid-\u03b2 by Microglia","volume":"287","author":"Yuyama","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"37405","DOI":"10.1074\/jbc.M110.149468","article-title":"Statins Promote the Degradation of Extracellular Amyloid \u03b2-Peptide by Microglia via Stimulation of Exosome-associated Insulin-degrading Enzyme (IDE) Secretion","volume":"285","author":"Tamboli","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1111\/bph.14585","article-title":"Mitochondrial dysfunction in Alzheimer\u2019s disease: Role in pathogenesis and novel therapeutic opportunities","volume":"176","author":"Ortiz","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/j.bbadis.2013.09.010","article-title":"The Alzheimer\u2019s disease mitochondrial cascade hypothesis: Progress and perspectives","volume":"1842","author":"Swerdlow","year":"2014","journal-title":"Biochim. Biophys. Acta BBA Mol. Basis Dis."},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.brainresrev.2005.03.004","article-title":"Are mitochondria critical in the pathogenesis of Alzheimer\u2019s disease?","volume":"49","author":"Reddy","year":"2005","journal-title":"Brain Res. Rev."},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"679","DOI":"10.5483\/BMBRep.2019.52.12.282","article-title":"The role of cell type-specific mitochondrial dysfunction in the pathogenesis of Alzheimer\u2019s disease","volume":"52","author":"Kim","year":"2019","journal-title":"BMB Rep."},{"key":"ref_308","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.tips.2015.03.002","article-title":"Amyloid biomarkers in Alzheimer\u2019s disease","volume":"36","author":"Blennow","year":"2015","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/ana.410420114","article-title":"Metabolic reduction in the posterior cingulate cortex in very early Alzheimer\u2019s disease","volume":"42","author":"Minoshima","year":"1997","journal-title":"Ann. Neurol."},{"key":"ref_310","first-page":"5148","article-title":"Protective effects of reduced dynamin-related protein 1 against amyloid beta-induced mitochondrial dysfunction and synaptic damage in Alzheimer\u2019s disease","volume":"25","author":"Manczak","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1093\/hmg\/ddy042","article-title":"Hippocampal mutant APP and amyloid beta-induced cognitive decline, dendritic spine loss, defective autophagy, mitophagy and mitochondrial abnormalities in a mouse model of Alzheimer\u2019s disease","volume":"27","author":"Manczak","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1093\/hmg\/ddx381","article-title":"Hippocampal phosphorylated tau induced cognitive decline, dendritic spine loss and mitochondrial abnormalities in a mouse model of Alzheimer\u2019s disease","volume":"27","author":"Kandimalla","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_313","doi-asserted-by":"crossref","first-page":"19318","DOI":"10.1073\/pnas.0804871105","article-title":"Amyloid- overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission\/fusion proteins","volume":"105","author":"Wang","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1111\/j.1471-4159.2011.07581.x","article-title":"Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer\u2019s disease","volume":"120","author":"Sheng","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"536","DOI":"10.3389\/fimmu.2018.00536","article-title":"Mitochondria: An Organelle of Bacterial Origin Controlling Inflammation","volume":"9","author":"Meyer","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.mito.2013.01.003","article-title":"Mitochondrial dysfunction and the inflammatory response","volume":"13","year":"2013","journal-title":"Mitochondrion"},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1002\/glia.23587","article-title":"Lipopolysaccharide-induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo","volume":"67","author":"Nair","year":"2019","journal-title":"Glia"},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"493.e6","DOI":"10.1016\/j.cmet.2019.06.005","article-title":"A Breakdown in Metabolic Reprogramming Causes Microglia Dysfunction in Alzheimer\u2019s Disease","volume":"30","author":"Baik","year":"2019","journal-title":"Cell Metab."},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.cell.2017.07.023","article-title":"TREM2 Maintains Microglial Metabolic Fitness in Alzheimer\u2019s Disease","volume":"170","author":"Ulland","year":"2017","journal-title":"Cell"},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/s41593-018-0332-9","article-title":"Mitophagy inhibits amyloid-\u03b2 and tau pathology and reverses cognitive deficits in models of Alzheimer\u2019s disease","volume":"22","author":"Fang","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"104469","DOI":"10.1016\/j.neuint.2019.104469","article-title":"Microglial mitophagy mitigates neuroinflammation in Alzheimer\u2019s disease","volume":"129","author":"Lautrup","year":"2019","journal-title":"Neurochem. Int."},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3389\/fnagi.2020.00252","article-title":"Mitochondrial Dysfunction and Alzheimer\u2019s Disease: Role of Microglia","volume":"12","author":"Agrawal","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_324","first-page":"674","article-title":"NLRP3 is activated in Alzheimer\u2019s disease and contributes to pathology in APP\/PS1 mice","volume":"493","author":"Heneka","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_325","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1021\/acschemneuro.9b00117","article-title":"Interplay between Mitophagy and Inflammasomes in Neurological Disorders","volume":"10","author":"Kesharwani","year":"2019","journal-title":"ACS Chem. 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