{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:10:17Z","timestamp":1787793017647,"version":"build-2784847793"},"reference-count":218,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Inflammation plays a large role in the etiology of the late onset, sporadic form of Alzheimer\u2019s disease (AD), yet these critical factors are not adequately modeled in mice where inflammatory mechanisms often differ widely from primates. In contrast, aging rhesus macaques offer a powerful translational model for investigating how advancing age and inflammation initiate early-stage pathology in sporadic AD, and for evaluating preventive therapeutic strategies. Unlike rodents, macaques possess highly developed association cortices with magnified calcium signaling, human-like inflammatory responses, and are naturally homozygous for ApoE-\u03b54\u2014factors that together contribute to the spontaneous emergence of tau and amyloid pathology alongside cognitive decline. Critically, macaques allow the detection of early, soluble forms of hyperphosphorylated tau (pTau), including pT217Tau, which rapidly dephosphorylates postmortem and is rarely observable in human brain tissue outside of biopsies. New findings reveal that soluble pTau is neurotoxic and capable of propagating pathology across cortical networks, with elevated pT217Tau in plasma. Growing evidence points to age-related inflammatory signaling as a key driver of calcium dysregulation, which in turn promotes tau hyperphosphorylation, amyloid-\u03b2 (A\u03b2) accumulation, synapse loss and autophagic degeneration. Both GCPII (glutamate carboxypeptidase II) and kynurenic acid inflammatory signaling have expanded roles in the primate association cortices that contribute to cognitive deficits. Pharmacological interventions in aged macaques demonstrate that targeting inflammation and restoring calcium homeostasis can significantly reduce pTau pathology with minimal side effects\u2014highlighting a promising path for early intervention in AD.<\/jats:p>","DOI":"10.3389\/fncel.2026.1750092","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T07:14:30Z","timestamp":1770880470000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Inflammatory mechanisms underlying early Alzheimer\u2019s disease pathology: evidence from the aging rhesus macaque brain"],"prefix":"10.3389","volume":"20","author":[{"given":"Dibyadeep","family":"Datta","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Yale Medical School","place":["New Haven, CT, United States"]},{"name":"Department of Neuroscience, Yale Medical School","place":["New Haven, CT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Yale Medical School","place":["New Haven, CT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy F. 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Med."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e12431","DOI":"10.1002\/trc2.12431","article-title":"Chronic GCPII (glutamate-carboxypeptidase-II) inhibition reduces pT217Tau levels in the entorhinal and dorsolateral prefrontal cortices of aged macaques","volume":"9","author":"Bathla","year":"2023","journal-title":"Alzheimers Dement (N Y)"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"607691","DOI":"10.3389\/fimmu.2021.607691","article-title":"T cells actively infiltrate the white matter of the aging monkey brain in relation to increased microglial reactivity and cognitive decline","volume":"12","author":"Batterman","year":"2021","journal-title":"Front. Immunol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1002\/cne.903210206","article-title":"Heterogeneity of layer II neurons in human entorhinal cortex","volume":"321","author":"Beall","year":"1992","journal-title":"J. Comp. 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USA"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/341230a0","article-title":"NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus","volume":"341","author":"Bekkers","year":"1989","journal-title":"Nature"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"2198","DOI":"10.1073\/pnas.0711074105","article-title":"Remodeling of ryanodine receptor complex causes \"leaky\" channels: a molecular mechanism for decreased exercise capacity","volume":"105","author":"Bellinger","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/s41582-021-00549-x","article-title":"Peripheral and central immune system crosstalk in Alzheimer disease - a research prospectus","volume":"17","author":"Bettcher","year":"2021","journal-title":"Nat. Rev. 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Anat. Embryol. Cell Biol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1007\/s00401-011-0825-z","article-title":"Alzheimer's pathogenesis: is there neuron-to-neuron propagation?","volume":"121","author":"Braak","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2814","DOI":"10.1093\/brain\/awv236","article-title":"The preclinical phase of the pathological process underlying sporadic Alzheimer's disease","volume":"138","author":"Braak","year":"2015","journal-title":"Brain"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1097\/NEN.0b013e318232a379","article-title":"Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years","volume":"70","author":"Braak","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1007\/s12035-014-8657-1","article-title":"Body fluid cytokine levels in mild cognitive impairment and Alzheimer's disease: a comparative overview","volume":"50","author":"Brosseron","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/mp.2011.24","article-title":"Alzheimer risk associated with a copy number variation in the complement receptor 1 increasing C3b\/C4b binding sites","volume":"17","author":"Brouwers","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1001 e1","DOI":"10.1016\/j.neurobiolaging.2011.03.011","article-title":"Altered ryanodine receptor expression in mild cognitive impairment and Alzheimer's disease","volume":"33","author":"Bruno","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1038\/s41593-018-0195-0","article-title":"Hierarchy of transcriptomic specialization across human cortex captured by structural neuroimaging topography","volume":"21","author":"Burt","year":"2018","journal-title":"Nature Neurosci"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1038\/s41593-017-0011-2","article-title":"A multiregional proteomic survey of the postnatal human brain","volume":"20","author":"Carlyle","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"5036","DOI":"10.1073\/pnas.1322360111","article-title":"cAMP-PKA phosphorylation of tau confers risk for degeneration in aging association cortex","volume":"111","author":"Carlyle","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"9458","DOI":"10.1523\/JNEUROSCI.2047-09.2009","article-title":"Deviant ryanodine receptor-mediated calcium release resets synaptic homeostasis in presymptomatic 3xTg-AD mice","volume":"29","author":"Chakroborty","year":"2009","journal-title":"J. Neurosci."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1186\/s12974-019-1567-4","article-title":"Plasma neurofilament light chain and amyloid-\u03b2 are associated with the kynurenine pathway metabolites in preclinical Alzheimer\u2019s disease","volume":"16","author":"Chatterjee","year":"2019","journal-title":"J. Neuroinflammation"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"ra22","DOI":"10.1126\/scisignal.2000818","article-title":"Gain-of-function enhancement of IP3 receptor modal gating by familial Alzheimer's disease-linked presenilin mutants in human cells and mouse neurons","volume":"3","author":"Cheung","year":"2010","journal-title":"Sci. Signal."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1038\/s41593-022-01197-0","article-title":"Multiregion transcriptomic profiling of the primate brain reveals signatures of aging and the social environment","volume":"25","author":"Chiou","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"7552","DOI":"10.1038\/s41467-023-42819-w","article-title":"INPP5D regulates inflammasome activation in human microglia","volume":"14","author":"Chou","year":"2023","journal-title":"Nat. Commun."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.biopsych.2017.10.007","article-title":"Microglia-mediated neuroprotection, TREM2, and Alzheimer's disease: evidence from optical imaging","volume":"83","author":"Condello","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/s41582-023-00883-2","article-title":"Tau-targeting therapies for Alzheimer disease: current status and future directions","volume":"19","author":"Congdon","year":"2023","journal-title":"Nat. Rev. Neurol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"5895","DOI":"10.1113\/jphysiol.2013.260521","article-title":"Redox modification of ryanodine receptors by mitochondria-derived reactive oxygen species contributes to aberrant Ca2+ handling in ageing rabbit hearts","volume":"591","author":"Cooper","year":"2013","journal-title":"J. Physiol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/ng0694-180","article-title":"Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease","volume":"7","author":"Corder","year":"1994","journal-title":"Nat. Genet."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.imbio.2011.07.017","article-title":"Complement receptor 1 (CR1) and Alzheimer's disease","volume":"217","author":"Crehan","year":"2012","journal-title":"Immunobiology"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1002\/acn3.51825","article-title":"The kynurenine pathway relates to post-acute COVID-19 objective cognitive impairment and PASC","volume":"10","author":"Cysique","year":"2023","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1002\/glia.24355","article-title":"Complement receptor 1 is expressed on brain cells and in the human brain","volume":"71","author":"Daskoulidou","year":"2023","journal-title":"Glia"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.1021\/acschemneuro.7b00505","article-title":"Unique molecular regulation of higher-order prefrontal cortical circuits: insights into the neurobiology of schizophrenia","volume":"9","author":"Datta","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"ref55","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci9050113","article-title":"Loss of prefrontal cortical higher cognition with uncontrollable stress: molecular mechanisms, changes with age, and relevance to treatment","volume":"9","author":"Datta","year":"2019","journal-title":"Brain Sci."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"e14477","DOI":"10.1002\/alz.14477","article-title":"The etiology and prevention of early-stage tau pathology in higher cortical circuits: insights from aging rhesus macaques","volume":"21","author":"Datta","year":"2025","journal-title":"Alzheimers Dement."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"578483","DOI":"10.3389\/fnana.2020.578483","article-title":"Mapping phosphodiesterase 4D (PDE4D) in macaque dorsolateral prefrontal cortex: postsynaptic compartmentalization in layer III pyramidal cell circuits","volume":"14","author":"Datta","year":"2020","journal-title":"Front. Neuroanat."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s12974-019-1683-1","article-title":"Classical complement cascade initiating C1q protein within neurons in the aged rhesus macaque dorsolateral prefrontal cortex","volume":"17","author":"Datta","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1002\/alz.12325","article-title":"Age-related calcium dysregulation linked with tau pathology and impaired cognition in non-human primates","volume":"17","author":"Datta","year":"2021","journal-title":"Alzheimers Dement."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"760270","DOI":"10.3389\/fnagi.2021.760270","article-title":"Glutamate carboxypeptidase II in aging rat prefrontal cortex impairs working memory performance","volume":"13","author":"Datta","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"11501","DOI":"10.1093\/cercor\/bhad382","article-title":"Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer's disease","volume":"33","author":"Datta","year":"2023","journal-title":"Cereb. Cortex"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"2843","DOI":"10.1002\/alz.13737","article-title":"Nanoscale imaging of pT217-tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: evidence of interneuronal trafficking and early-stage neurodegeneration","volume":"20","author":"Datta","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"2722","DOI":"10.1523\/JNEUROSCI.2472-18.2019","article-title":"Noradrenergic alpha1-Adrenoceptor actions in the primate dorsolateral prefrontal cortex","volume":"39","author":"Datta","year":"2019","journal-title":"J. Neurosci."},{"key":"ref64","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2024.1112","article-title":"Key roles of CACNA1C\/Cav1.2 and CALB1\/Calbindin in prefrontal neurons altered in cognitive disorders","author":"Datta","year":"2024","journal-title":"JAMA Psychiatr."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"100589","DOI":"10.1016\/j.xgen.2024.100589","article-title":"Evolutionary and biomedical implications of sex differences in the primate brain transcriptome","volume":"4","author":"DeCasien","year":"2024","journal-title":"Cell Genom."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1016\/j.cell.2018.05.003","article-title":"Disease-associated microglia: a universal immune sensor of neurodegeneration","volume":"173","author":"Deczkowska","year":"2018","journal-title":"Cell"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1016\/j.cell.2020.05.003","article-title":"The physiology, pathology, and potential therapeutic applications of the TREM2 signaling pathway","volume":"181","author":"Deczkowska","year":"2020","journal-title":"Cell"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"29","DOI":"10.3389\/fnana.2011.00029","article-title":"The evolution of the brain, the human nature of cortical circuits, and intellectual creativity","volume":"5","author":"Defelipe","year":"2011","journal-title":"Front. Neuroanat."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1002\/ana.410270502","article-title":"Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity","volume":"27","author":"DeKosky","year":"1990","journal-title":"Ann. Neurol."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1016\/j.cell.2008.05.048","article-title":"A polymorphism in CALHM1 influences Ca2+ homeostasis, Abeta levels, and Alzheimer's disease risk","volume":"133","author":"Dreses-Werringloer","year":"2008","journal-title":"Cell"},{"key":"ref71","doi-asserted-by":"publisher","DOI":"10.3390\/cells10051138","article-title":"Microglia in aging and Alzheimer's disease: a comparative species review","volume":"10","author":"Edler","year":"2021","journal-title":"Cells"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"30322","DOI":"10.1074\/jbc.274.42.30322","article-title":"Activation of the L voltage-sensitive calcium channel by mitogen-activated protein (MAP) kinase following exposure of neuronal cells to beta-amyloid. MAP kinase mediates beta-amyloid-induced neurodegeneration","volume":"274","author":"Ekinci","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"RC95","DOI":"10.1523\/jneurosci.20-18-j0002.2000","article-title":"Pyramidal cells of the frontal lobe: all the more spinous to think with","volume":"20","author":"Elston","year":"2000","journal-title":"J. Neurosci."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1093\/cercor\/bhg093","article-title":"Cortex, cognition and the cell: new insights into the pyramidal neuron and prefrontal function","volume":"13","author":"Elston","year":"2003","journal-title":"Cereb. Cortex"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"RC163","DOI":"10.1523\/JNEUROSCI.21-17-j0002.2001","article-title":"The pyramidal cell in cognition: a comparative study in human and monkey","volume":"21","author":"Elston","year":"2001","journal-title":"J. Neurosci."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3389\/fnana.2011.00002","article-title":"Pyramidal cells in prefrontal cortex of primates: marked differences in neuronal structure among species","volume":"5","author":"Elston","year":"2011","journal-title":"Front. Neuroanat."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1002\/ar.a.20278","article-title":"Specializations of the granular prefrontal cortex of primates: implications for cognitive processing","volume":"288","author":"Elston","year":"2006","journal-title":"Anat Rec A Discov Mol Cell Evol Biol"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"5216","DOI":"10.1093\/cercor\/bhac009","article-title":"Differential gene expression in layer 3 pyramidal neurons across 3 regions of the human cortical visual spatial working memory network","volume":"32","author":"Enwright","year":"2022","journal-title":"Cereb. Cortex"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.biopsych.2004.10.034","article-title":"Molecular aging in human prefrontal cortex is selective and continuous throughout adult life","volume":"57","author":"Erraji-Benchekroun","year":"2005","journal-title":"Biol. Psychiatry"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13024-024-00734-8","article-title":"Alzheimer's disease associated isoforms of human CD33 distinctively modulate microglial cell responses in 5XFAD mice","volume":"19","author":"Eskandari-Sedighi","year":"2024","journal-title":"Mol. 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Ther."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41586-019-1895-7","article-title":"Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease","volume":"577","author":"Gate","year":"2020","journal-title":"Nature"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1016\/j.cell.2019.11.010","article-title":"Cross-species single-cell analysis reveals divergence of the primate microglia program","volume":"179","author":"Geirsdottir","year":"2019","journal-title":"Cell"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1212\/01.wnl.0000063311.58879.01","article-title":"Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease","volume":"60","author":"Giannakopoulos","year":"2003","journal-title":"Neurology"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1001\/jamaneurol.2018.2505","article-title":"Mechanisms of cell-to-cell transmission of pathological tau: a review","volume":"76","author":"Gibbons","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1007\/s11064-017-2182-3","article-title":"Interactions of mitochondria\/metabolism and calcium regulation in Alzheimer's disease: a Calcinist point of view","volume":"42","author":"Gibson","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/cercor\/bhw062","article-title":"Area-specific features of pyramidal neurons-a comparative study in mouse and Rhesus monkey","volume":"27","author":"Gilman","year":"2017","journal-title":"Cereb. Cortex"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/bs.ircmb.2018.05.006","article-title":"Mitochondria and reactive oxygen species in aging and age-related diseases","volume":"340","author":"Giorgi","year":"2018","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1001\/archpsyc.57.1.65","article-title":"Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia","volume":"57","author":"Glantz","year":"2000","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1212\/wnl.0000000000003234","article-title":"Relative effect of APOE \u03b54 on neuroimaging biomarker changes across the lifespan","volume":"87","author":"Gonneaud","year":"2016","journal-title":"Neurology"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"12128","DOI":"10.1523\/JNEUROSCI.2474-10.2010","article-title":"NMDA-mediated ca(2+) influx drives aberrant ryanodine receptor activation in dendrites of young Alzheimer's disease mice","volume":"30","author":"Goussakov","year":"2010","journal-title":"J. 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Neurol."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"a006312","DOI":"10.1101\/cshperspect.a006312","article-title":"Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease","volume":"2","author":"Holtzman","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1126\/science.6474172","article-title":"Alzheimer's disease: cell-specific pathology isolates the hippocampal formation","volume":"225","author":"Hyman","year":"1984","journal-title":"Science"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"106375","DOI":"10.1016\/j.isci.2023.106375","article-title":"INPP5D modulates TREM2 loss-of-function phenotypes in a \u03b2-amyloidosis mouse model","volume":"26","author":"Iguchi","year":"2023","journal-title":"iScience"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1093\/cercor\/bhx005","article-title":"mGluR2 versus mGluR3 metabotropic glutamate receptors in primate dorsolateral prefrontal cortex: postsynaptic mGluR3 strengthen working memory networks","volume":"28","author":"Jin","year":"2018","journal-title":"Cereb. Cortex"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1038\/mp.2016.129","article-title":"mGluR2\/3 mechanisms in primate dorsolateral prefrontal cortex: evidence for both presynaptic and postsynaptic actions","volume":"22","author":"Jin","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref108","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1038\/s41593-023-01415-3","article-title":"Infiltrating CD8(+) T cells exacerbate Alzheimer's disease pathology in a 3D human neuroimmune axis model","volume":"26","author":"Jorfi","year":"2023","journal-title":"Nat. Neurosci."},{"key":"ref109","doi-asserted-by":"publisher","first-page":"8306","DOI":"10.1523\/JNEUROSCI.0860-20.2020","article-title":"Serial prefrontal pathways are positioned to balance cognition and emotion in Primates","volume":"40","author":"Joyce","year":"2020","journal-title":"J. Neurosci."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s00401-018-1855-6","article-title":"Tau seeding activity begins in the transentorhinal\/entorhinal regions and anticipates phospho-tau pathology in Alzheimer's disease and PART","volume":"136","author":"Kaufman","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/s0306-4522(99)00042-1","article-title":"Alterations in the ryanodine receptor calcium release channel correlate with Alzheimer's disease neurofibrillary and beta-amyloid pathologies","volume":"92","author":"Kelliher","year":"1999","journal-title":"Neuroscience"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1097\/00002093-199100051-00002","article-title":"Overview of basic research on Alzheimer disease: implications for cognition","volume":"5","author":"Khachaturian","year":"1991","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref113","doi-asserted-by":"publisher","first-page":"2860","DOI":"10.1038\/s41380-019-0401-9","article-title":"Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia","volume":"25","author":"Kindler","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref114","doi-asserted-by":"publisher","first-page":"S13","DOI":"10.1038\/d41586-018-05722-9","article-title":"The search for better animal models of Alzheimer's disease","volume":"559","author":"King","year":"2018","journal-title":"Nature"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.3233\/jad-170255","article-title":"Of mice and men: comparative analysis of neuro-inflammatory mechanisms in human and mouse using cause-and-effect models","volume":"59","author":"Kodamullil","year":"2017","journal-title":"J Alzheimer's Dis"},{"key":"ref116","doi-asserted-by":"crossref","first-page":"4197","DOI":"10.1046\/j.1460-9568.1999.00844.x","article-title":"Neurochemical gradients along monkey sensory cortical pathways: calbindin-immunoreactive pyramidal neurons in layers II and III","volume":"11","author":"Kondo","year":"1999","journal-title":"Eur. J. Neurosci."},{"key":"ref117","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s00439-018-1883-2","article-title":"Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer's disease","volume":"137","author":"Kucukkilic","year":"2018","journal-title":"Hum. Genet."},{"key":"ref118","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1007\/s00401-017-1733-7","article-title":"Post-translational remodeling of ryanodine receptor induces calcium leak leading to Alzheimer's disease-like pathologies and cognitive deficits","volume":"134","author":"Lacampagne","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref119","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nrn2168","article-title":"Intracellular amyloid-beta in Alzheimer's disease","volume":"8","author":"LaFerla","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"ref120","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s13024-020-00382-8","article-title":"Sex-dependent calcium hyperactivity due to lysosomal-related dysfunction in astrocytes from APOE4 versus APOE3 gene targeted replacement mice","volume":"15","author":"Larramona-Arcas","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref121","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1523\/jneurosci.07-06-01799.1987","article-title":"Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: a quantitative study of visual and auditory cortices","volume":"7","author":"Lewis","year":"1987","journal-title":"J. Neurosci."},{"key":"ref122","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23137273","article-title":"Oxidative stress in ageing and chronic degenerative pathologies: molecular mechanisms involved in counteracting oxidative stress and chronic inflammation","volume":"23","author":"Leyane","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref123","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1016\/j.celrep.2017.10.006","article-title":"Suppressed Calbindin levels in hippocampal excitatory neurons mediate stress-induced memory loss","volume":"21","author":"Li","year":"2017","journal-title":"Cell Rep."},{"key":"ref124","doi-asserted-by":"publisher","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":"ref125","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1016\/j.neuron.2025.03.034","article-title":"CLU alleviates Alzheimer's disease-relevant processes by modulating astrocyte reactivity and microglia-dependent synaptic density","volume":"113","author":"Lish","year":"2025","journal-title":"Neuron"},{"key":"ref126","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1016\/j.neuron.2017.11.013","article-title":"ApoE4 accelerates early seeding of amyloid pathology","volume":"96","author":"Liu","year":"2017","journal-title":"Neuron"},{"key":"ref127","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1042\/BJ20101184","article-title":"Phosphorylation of cAMP-specific PDE4A5 (phosphodiesterase-4A5) by MK2 (MAPKAPK2) attenuates its activation through protein kinase a phosphorylation","volume":"435","author":"MacKenzie","year":"2011","journal-title":"Biochem. J."},{"key":"ref128","doi-asserted-by":"publisher","first-page":"bhae174","DOI":"10.1093\/cercor\/bhae174","article-title":"The meso-connectomes of mouse, marmoset, and macaque: network organization and the emergence of higher cognition","volume":"34","author":"Magrou","year":"2024","journal-title":"Cereb. Cortex"},{"key":"ref129","doi-asserted-by":"publisher","first-page":"13320","DOI":"10.1523\/JNEUROSCI.1224-13.2013","article-title":"CD33 Alzheimer's risk-altering polymorphism, CD33 expression, and exon 2 splicing","volume":"33","author":"Malik","year":"2013","journal-title":"J. Neurosci."},{"key":"ref130","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/s0962-8924(98)01368-3","article-title":"Tau in Alzheimer's disease","volume":"8","author":"Mandelkow","year":"1998","journal-title":"Trends Cell Biol."},{"key":"ref131","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1016\/j.neuron.2022.03.004","article-title":"ApoE Cascade hypothesis in the pathogenesis of Alzheimer's disease and related dementias","volume":"110","author":"Martens","year":"2022","journal-title":"Neuron"},{"key":"ref132","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0092-8674(00)80847-8","article-title":"PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts","volume":"101","author":"Marx","year":"2000","journal-title":"Cell"},{"key":"ref133","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/0896-6273(94)90264-x","article-title":"Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer's disease paired helical filament tau","volume":"13","author":"Matsuo","year":"1994","journal-title":"Neuron"},{"key":"ref134","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1111\/j.1474-9726.2007.00275.x","article-title":"Calcium and neurodegeneration","volume":"6","author":"Mattson","year":"2007","journal-title":"Aging Cell"},{"key":"ref135","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1007\/s00415-023-12148-5","article-title":"Head-to-head study of diagnostic accuracy of plasma and cerebrospinal fluid p-tau217 versus p-tau181 and p-tau231 in a memory clinic cohort","volume":"271","author":"Mendes","year":"2024","journal-title":"J. Neurol."},{"key":"ref136","doi-asserted-by":"publisher","first-page":"1828","DOI":"10.1093\/brain\/awy103","article-title":"Longitudinal brain imaging in preclinical Alzheimer disease: impact of APOE \u03b54 genotype","volume":"141","author":"Mishra","year":"2018","journal-title":"Brain"},{"key":"ref137","doi-asserted-by":"publisher","first-page":"R1442","DOI":"10.1016\/j.cub.2020.10.009","article-title":"Anterior cingulate cortex and the control of dynamic behavior in primates","volume":"30","author":"Monosov","year":"2020","journal-title":"Current Bio"},{"key":"ref138","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glad254","article-title":"Differences in Alzheimer's disease-related pathology profiles across apolipoprotein groups","volume":"79","author":"Morrison","year":"2024","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref139","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/0197-4580(94)00064-6","article-title":"Apolipoprotein E-immunoreactivity in aged rhesus monkey cortex: colocalization with amyloid plaques","volume":"15","author":"Mufson","year":"1994","journal-title":"Neurobiol. Aging"},{"key":"ref140","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1093\/cercor\/bht354","article-title":"Analysis of synaptic gene expression in the neocortex of primates reveals evolutionary changes in glutamatergic neurotransmission","volume":"25","author":"Muntan\u00e9","year":"2015","journal-title":"Cereb. Cortex"},{"key":"ref141","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.neuroimage.2013.04.048","article-title":"Disease neuroimaging: mapping the effects of ApoE4, age and cognitive status on 18F-florbetapir PET measured regional cortical patterns of beta-amyloid density and growth","volume":"78","author":"Murphy","year":"2013","journal-title":"NeuroImage"},{"key":"ref142","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1038\/nn.3862","article-title":"A hierarchy of intrinsic timescales across primate cortex","volume":"17","author":"Murray","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref143","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1097\/NEN.0b013e31825018f7","article-title":"Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature","volume":"71","author":"Nelson","year":"2012","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref144","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.3389\/fphys.2018.01775","article-title":"Redox dependent modifications of ryanodine receptor: basic mechanisms and implications in heart diseases","volume":"9","author":"Nikolaienko","year":"2018","journal-title":"Front. Physiol."},{"key":"ref145","doi-asserted-by":"publisher","first-page":"e12268","DOI":"10.1002\/trc2.12268","article-title":"Treatment with glucagon-like peptide-1 receptor agonists and incidence of dementia: data from pooled double-blind randomized controlled trials and nationwide disease and prescription registers","volume":"8","author":"Norgaard","year":"2022","journal-title":"Alzheimers Dement (N Y)"},{"key":"ref146","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1038\/307462a0","article-title":"Magnesium gates glutamate-activated channels in mouse central neurones","volume":"307","author":"Nowak","year":"1984","journal-title":"Nature"},{"key":"ref147","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.neuron.2019.12.007","article-title":"TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge","volume":"105","author":"Nugent","year":"2020","journal-title":"Neuron"},{"key":"ref148","doi-asserted-by":"publisher","first-page":"3046","DOI":"10.1074\/jbc.M005070200","article-title":"Apolipoprotein E4 stimulates cAMP response element-binding protein transcriptional activity through the extracellular signal-regulated kinase pathway","volume":"276","author":"Ohkubo","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref149","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1042\/bss0670121","article-title":"Apolipoprotein E and beta A4-amyloid: signals and effects","volume":"67","author":"Ohm","year":"2001","journal-title":"Biochem. Soc. Symp."},{"key":"ref150","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1007\/s11064-017-2181-4","article-title":"NAAG peptidase inhibitors act via mGluR3: animal models of memory, Alzheimer's, and ethanol intoxication","volume":"42","author":"Olszewski","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref151","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1176\/appi.ajp.20240048","article-title":"Kynurenic acid and promotion of activity-dependent synapse elimination in schizophrenia","volume":"182","author":"Orhan","year":"2025","journal-title":"Am. J. Psychiatry"},{"key":"ref152","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1001\/jama.2020.12134","article-title":"Discriminative accuracy of plasma Phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders","volume":"324","author":"Palmqvist","year":"2020","journal-title":"JAMA"},{"key":"ref153","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13195-024-01655-w","article-title":"Plasma phospho-tau217 as a predictive biomarker for Alzheimer's disease in a large south American cohort","volume":"17","author":"Pandey","year":"2025","journal-title":"Alzheimer's Res Ther"},{"key":"ref154","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/s41593-018-0296-9","article-title":"Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE","volume":"22","author":"Parhizkar","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref155","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.jalz.2017.11.005","article-title":"The aged rhesus macaque manifests Braak stage III\/IV Alzheimer's-like pathology","volume":"14","author":"Paspalas","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref156","doi-asserted-by":"publisher","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":"ref157","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010778","article-title":"Apoe4 and Alzheimer's disease pathogenesis-mitochondrial deregulation and targeted therapeutic strategies","volume":"24","author":"Pires","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref158","doi-asserted-by":"publisher","first-page":"10709","DOI":"10.1073\/pnas.1201894109","article-title":"Human brain evolution: from gene discovery to phenotype discovery","author":"Preuss","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref159","doi-asserted-by":"publisher","first-page":"8686","DOI":"10.1523\/JNEUROSCI.0435-21.2021","article-title":"APOE4 affects basal and NMDAR-mediated protein synthesis in neurons by perturbing calcium homeostasis","volume":"41","author":"Ramakrishna","year":"2021","journal-title":"J. Neurosci."},{"key":"ref160","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/s0896-6273(03)00694-9","article-title":"Dysregulation of protein kinase a signaling in the aged prefrontal cortex: new strategy for treating age-related cognitive decline","volume":"40","author":"Ramos","year":"2003","journal-title":"Neuron"},{"key":"ref161","doi-asserted-by":"publisher","first-page":"3568","DOI":"10.1523\/jneurosci.09-10-03568.1989","article-title":"Evidence for task-dependent memory dysfunction in the aged monkey","volume":"9","author":"Rapp","year":"1989","journal-title":"J. Neurosci."},{"key":"ref162","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/s41586-020-2156-5","article-title":"LRP1 is a master regulator of tau uptake and spread","volume":"580","author":"Rauch","year":"2020","journal-title":"Nature"},{"key":"ref163","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s13024-022-00574-4","article-title":"ApoE in Alzheimer's disease: pathophysiology and therapeutic strategies","volume":"17","author":"Raulin","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref164","doi-asserted-by":"publisher","first-page":"289","DOI":"10.2217\/nmt-2021-0022","article-title":"NM101 phase III study of NE3107 in Alzheimer's disease: rationale, design and therapeutic modulation of neuroinflammation and insulin resistance","volume":"11","author":"Reading","year":"2021","journal-title":"Neurodegener Dis Manag"},{"key":"ref165","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1002\/alz.12558","article-title":"Alzheimer's-like signaling in brains of COVID-19 patients","volume":"18","author":"Reiken","year":"2022","journal-title":"Alzheimers Dement."},{"key":"ref166","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1172\/JCI20640","article-title":"Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology","volume":"114","author":"Rissman","year":"2004","journal-title":"J. Clin. Invest."},{"key":"ref167","doi-asserted-by":"publisher","first-page":"315","DOI":"10.3389\/fnagi.2016.00315","article-title":"Evidence of tau hyperphosphorylation and dystrophic microglia in the common marmoset","volume":"8","author":"Rodriguez-Callejas","year":"2016","journal-title":"Front. Aging Neurosci."},{"key":"ref168","doi-asserted-by":"publisher","first-page":"2990","DOI":"10.1038\/s41591-024-03122-3","article-title":"Sex-dependent APOE4 neutrophil-microglia interactions drive cognitive impairment in Alzheimer's disease","volume":"30","author":"Rosenzweig","year":"2024","journal-title":"Nat. Med."},{"key":"ref169","doi-asserted-by":"publisher","first-page":"6454","DOI":"10.1038\/s41467-023-42096-7","article-title":"Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction","volume":"14","author":"Sabogal-Guaqueta","year":"2023","journal-title":"Nat. Commun."},{"key":"ref170","doi-asserted-by":"publisher","first-page":"4908","DOI":"10.1002\/alz.13089","article-title":"The Alzheimer's disease risk factor INPP5D restricts neuroprotective microglial responses in amyloid beta-mediated pathology","volume":"19","author":"Samuels","year":"2023","journal-title":"Alzheimers Dement."},{"key":"ref171","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/s0006-3223(01)01078-2","article-title":"Increased cortical kynurenate content in schizophrenia","volume":"50","author":"Schwarcz","year":"2001","journal-title":"Biol. Psychiatry"},{"key":"ref172","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1002\/ana.24369","article-title":"APOE\u03b52 is associated with milder clinical and pathological Alzheimer disease","volume":"77","author":"Serrano-Pozo","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref173","doi-asserted-by":"publisher","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":"ref174","doi-asserted-by":"publisher","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":"ref175","doi-asserted-by":"publisher","first-page":"2546","DOI":"10.1084\/jem.20190980","article-title":"Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model","volume":"216","author":"Shi","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref176","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.cell.2017.06.036","article-title":"Evolution of the human nervous system function, structure, and development","volume":"170","author":"Sousa","year":"2017","journal-title":"Cell"},{"key":"ref177","doi-asserted-by":"publisher","first-page":"166384","DOI":"10.1016\/j.bbadis.2022.166384","article-title":"Clusterin in Alzheimer's disease: An amyloidogenic inhibitor of amyloid formation?","volume":"1868","author":"Spatharas","year":"2022","journal-title":"Biochim. Biophys. Acta Mol. basis Dis."},{"key":"ref178","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1146\/annurev-neuro-061010-113810","article-title":"The complement system: an unexpected role in synaptic pruning during development and disease","volume":"35","author":"Stephan","year":"2012","journal-title":"Annu. Rev. Neurosci."},{"key":"ref179","doi-asserted-by":"publisher","first-page":"13460","DOI":"10.1523\/JNEUROSCI.1333-13.2013","article-title":"A dramatic increase of C1q protein in the CNS during normal aging","volume":"33","author":"Stephan","year":"2013","journal-title":"J. Neurosci."},{"key":"ref180","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/s0014-2999(02)01851-4","article-title":"The pharmacological manipulation of glutamate receptors and neuroprotection","volume":"447","author":"Stone","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref181","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.tips.2023.04.006","article-title":"Modulation of T cells by tryptophan metabolites in the kynurenine pathway","volume":"44","author":"Stone","year":"2023","journal-title":"Trends Pharmacol. Sci."},{"key":"ref182","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1073\/pnas.90.5.1977","article-title":"Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease","volume":"90","author":"Strittmatter","year":"1993","journal-title":"Proc. Natl. Acad. Sci. 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Neurosci."},{"key":"ref186","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1016\/j.biopsych.2010.06.012","article-title":"A meta-analysis of cytokines in Alzheimer's disease","volume":"68","author":"Swardfager","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref187","doi-asserted-by":"publisher","first-page":"9744","DOI":"10.1523\/JNEUROSCI.21-24-09744.2001","article-title":"Elevated postsynaptic [Ca2+]i and L-type calcium channel activity in aged hippocampal neurons: relationship to impaired synaptic plasticity","volume":"21","author":"Thibault","year":"2001","journal-title":"J. Neurosci."},{"key":"ref188","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1126\/science.272.5264.1017","article-title":"Increase in single L-type calcium channels in hippocampal neurons during aging","volume":"272","author":"Thibault","year":"1996","journal-title":"Science"},{"key":"ref189","doi-asserted-by":"publisher","first-page":"105303","DOI":"10.1016\/j.nbd.2021.105303","article-title":"INPP5D expression is associated with risk for Alzheimer's disease and induced by plaque-associated microglia","volume":"153","author":"Tsai","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref190","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1046\/j.1471-4159.1997.68010265.x","article-title":"Amyloid beta protein potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels: a possible involvement of free radicals","volume":"68","author":"Ueda","year":"1997","journal-title":"J. Neurochem."},{"key":"ref191","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/s41582-018-0072-1","article-title":"TREM2 - a key player in microglial biology and Alzheimer disease","volume":"14","author":"Ulland","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref192","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/j.neuron.2013.06.036","article-title":"Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer a\u03b2 oligomer bound to cellular prion protein","volume":"79","author":"Um","year":"2013","journal-title":"Neuron"},{"key":"ref193","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1111\/j.1749-6632.1993.tb23058.x","article-title":"The age of biosenescence and the incidence of cerebral beta-amyloidosis in aged captive rhesus monkeys","volume":"695","author":"Uno","year":"1993","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref194","doi-asserted-by":"publisher","first-page":"100013","DOI":"10.1016\/j.tjpad.2024.100013","article-title":"Microglial activation states and their implications for Alzheimer's disease","volume":"12","author":"Valiukas","year":"2025","journal-title":"J. Prev Alzheimers Dis."},{"key":"ref195","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in early Alzheimer's disease","volume":"388","author":"van Dyck","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref196","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1097\/YCO.0000000000000713","article-title":"A systematic review of neuropsychological and psychiatric sequalae of COVID-19: implications for treatment","volume":"34","author":"Vanderlind","year":"2021","journal-title":"Curr. Opin. Psychiatry"},{"key":"ref197","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/nn1846","article-title":"Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory","volume":"10","author":"Vijayraghavan","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref198","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13024-022-00549-5","article-title":"Calcium-dependent cytosolic phospholipase a(2) activation is implicated in neuroinflammation and oxidative stress associated with ApoE4","volume":"17","author":"Wang","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref199","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200785","article-title":"Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer's disease model","volume":"217","author":"Wang","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref200","doi-asserted-by":"publisher","first-page":"4153","DOI":"10.1016\/j.cell.2022.09.033","article-title":"TREM2 drives microglia response to amyloid-beta via SYK-dependent and -independent pathways","volume":"185","author":"Wang","year":"2022","journal-title":"Cell"},{"key":"ref201","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/j.neuron.2012.12.032","article-title":"NMDA receptors subserve persistent neuronal firing during working memory in dorsolateral prefrontal cortex","volume":"77","author":"Wang","year":"2013","journal-title":"Neuron"},{"key":"ref202","doi-asserted-by":"publisher","first-page":"15709","DOI":"10.1038\/srep15709","article-title":"Rapid alteration of protein phosphorylation during postmortem: implication in the study of protein phosphorylation","volume":"5","author":"Wang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref203","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/s007020050029","article-title":"Tryptophan degradation and immune activation in Alzheimer's disease","volume":"107","author":"Widner","year":"2000","journal-title":"J. Neural Transm."},{"key":"ref204","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.3233\/JAD-2010-091117","article-title":"L-type calcium channel CaV 1.2 in transgenic mice overexpressing human AbetaPP751 with the London (V717I) and Swedish (K670M\/N671L) mutations","volume":"20","author":"Willis","year":"2010","journal-title":"J Alzheimer's Dis"},{"key":"ref205","doi-asserted-by":"publisher","first-page":"849937","DOI":"10.3389\/fnana.2022.849937","article-title":"Glutamate metabotropic receptor type 3 (mGlu3) localization in the rat Prelimbic medial prefrontal cortex","volume":"16","author":"Woo","year":"2022","journal-title":"Front. Neuroanat."},{"key":"ref206","doi-asserted-by":"publisher","first-page":"24705470211029254","DOI":"10.1177\/24705470211029254","article-title":"Chronic stress weakens connectivity in the prefrontal cortex: architectural and molecular changes","volume":"5","author":"Woo","year":"2021","journal-title":"Chronic Stress (Thousand Oaks)"},{"key":"ref207","doi-asserted-by":"publisher","first-page":"4252","DOI":"10.1038\/s41380-022-01656-x","article-title":"Inhibition of glutamate-carboxypeptidase-II in dorsolateral prefrontal cortex: potential therapeutic target for neuroinflammatory cognitive disorders","volume":"27","author":"Yang","year":"2022","journal-title":"Mol. 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Immunol."},{"key":"ref211","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.neuroscience.2014.05.008","article-title":"Differential effects of aging on dendritic spines in visual cortex and prefrontal cortex of the rhesus monkey","volume":"274","author":"Young","year":"2014","journal-title":"Neuroscience"},{"key":"ref212","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1007\/s12035-012-8237-1","article-title":"The role of clusterin in Alzheimer's disease: pathways, pathogenesis, and therapy","volume":"45","author":"Yu","year":"2012","journal-title":"Mol. Neurobiol."},{"key":"ref213","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1038\/s41593-021-00851-3","article-title":"Neuronal ApoE upregulates MHC-I expression to drive selective neurodegeneration in Alzheimer's disease","volume":"24","author":"Zalocusky","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref214","doi-asserted-by":"publisher","first-page":"106461","DOI":"10.1016\/j.nbd.2024.106461","article-title":"T cell infiltration mediates neurodegeneration and cognitive decline in Alzheimer's disease","volume":"193","author":"Zeng","year":"2024","journal-title":"Neurobiol. Dis."},{"key":"ref215","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.nbd.2016.06.010","article-title":"Maternal inflammation leads to impaired glutamate homeostasis and up-regulation of glutamate carboxypeptidase II in activated microglia in the fetal\/newborn rabbit brain","volume":"94","author":"Zhang","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref216","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1523\/JNEUROSCI.1820-22.2022","article-title":"A gating mutation in ryanodine receptor type 2 rescues phenotypes of Alzheimer's disease mouse models by upregulating neuronal autophagy","volume":"43","author":"Zhang","year":"2023","journal-title":"J. Neurosci."},{"key":"ref217","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/s41392-023-01486-5","article-title":"Role of neuroinflammation in neurodegeneration development","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref218","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1176\/appi.ajp.2020.19111152","article-title":"Association of Missense Mutation in FOLH1 with decreased NAAG levels and impaired working memory circuitry and cognition","volume":"177","author":"Zink","year":"2020","journal-title":"Am. J. 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