{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T01:05:28Z","timestamp":1768871128000,"version":"3.49.0"},"reference-count":73,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T00:00:00Z","timestamp":1689984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Greece","award":["2022-050-0502-52525"],"award-info":[{"award-number":["2022-050-0502-52525"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Brain aging has been correlated with high metallothionein I-II (MT-I\/II) expression, iron and zinc dyshomeostasis, and A\u03b2 deposition in humans and experimental animals. In the present study, iron and zinc accumulation, the expression of MT-I\/II and A\u03b242, and their potential association with aging in the feline brain were assessed. Tissue sections from the temporal and frontal grey (GM) and white (WM) matter, hippocampus, thalamus, striatum, cerebellum, and dentate nucleus were examined histochemically for the presence of age-related histopathological lesions and iron deposits and distribution. We found, using a modified Perl\u2019s\/DAB method, two types of iron plaques that showed age-dependent accumulation in the temporal GM and WM and the thalamus, along with the age-dependent increment in cerebellar-myelin-associated iron. We also demonstrated an age-dependent increase in MT-I\/II immunoreactivity in the feline brain. In cats over 7 years old, A\u03b2 immunoreactivity was detected in vessel walls and neuronal somata; extracellular A\u03b2 deposits were also evident. Interestingly, A\u03b2-positive astrocytes were also observed in certain cases. ICP-MS analysis of brain content regarding iron and zinc concentrations showed no statistically significant association with age, but a mild increase in iron with age was noticed, while zinc levels were found to be higher in the Mature and Senior groups. Our findings reinforce the suggestion that cats could serve as a dependable natural animal model for brain aging and neurodegeneration; thus, they should be further investigated on the basis of metal ion concentration changes and their effects on aging.<\/jats:p>","DOI":"10.3390\/brainsci13071115","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:47:03Z","timestamp":1690159623000},"page":"1115","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Metallothionein I\/II Expression and Metal Ion Levels in Correlation with Amyloid Beta Deposits in the Aged Feline Brain"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7642-7946","authenticated-orcid":false,"given":"Emmanouela P.","family":"Apostolopoulou","sequence":"first","affiliation":[{"name":"Department of Pathology, Faculty of Health Sciences, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54627 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaos","family":"Raikos","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine & Toxicology, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Vlemmas","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Health Sciences, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54627 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Efstratios","family":"Michaelidis","sequence":"additional","affiliation":[{"name":"Laboratories of the 3rd Army Veterinary Hospital, Chemical Department, 57001 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0588-7256","authenticated-orcid":false,"given":"Georgia D.","family":"Brellou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Health Sciences, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54627 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1177\/1098612X14536176","article-title":"Longevity and mortality of cats attending primary care veterinary practices in England","volume":"17","author":"Church","year":"2015","journal-title":"J. Feline Med. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"612","DOI":"10.3389\/fnins.2018.00612","article-title":"Parkinson\u2019s Disease: Biomarkers, Treatment, and Risk Factors","volume":"12","author":"Emamzadeh","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"187","DOI":"10.2174\/1874609808666150201214955","article-title":"Vitamins in the prevention or delay of cognitive disability of aging","volume":"7","author":"Dror","year":"2014","journal-title":"Curr. Aging Sci."},{"key":"ref_4","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_5","unstructured":"Summers, B.A., Cummings, J.F., and de Lahunta, A. (1995). Veterinary Neuropathology, Mosby. [1st ed.]."},{"key":"ref_6","unstructured":"Brellou, D.G. (2006). Studies on the Histopathological Changes and Presence of Amyloid \u03b2 Protein (A\u03b2) Deposits in the Aged Feline Brain. [Ph.D. Thesis, Aristotle University of Thessaloniki]."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.cvsm.2014.07.008","article-title":"Aging in the canine and feline brain","volume":"44","author":"Vite","year":"2014","journal-title":"Vet. Clin. N. Am. Small Anim. Pract."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"684607","DOI":"10.3389\/fragi.2021.684607","article-title":"Neuropathology of Aging in Cats and its Similarities to Human Alzheimer\u2019s Disease","volume":"2","author":"Sordo","year":"2021","journal-title":"Front. Aging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.neurobiolaging.2007.07.015","article-title":"Blood-brain barrier, ageing and microvascular disease\u2014Systematic review and meta-analysis","volume":"30","author":"Farrall","year":"2009","journal-title":"Neurobiol. Aging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.neuron.2014.12.032","article-title":"Blood-brain barrier breakdown in the aging human hippocampus","volume":"85","author":"Montagne","year":"2015","journal-title":"Neuron"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"351","DOI":"10.3389\/fnagi.2019.00351","article-title":"Regional Distributions of Iron, Copper and Zinc and Their Relationships with Glia in a Normal Aging Mouse Model","volume":"11","author":"Ashraf","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/978-981-13-9913-8_8","article-title":"Neuroglia in Ageing","volume":"1175","author":"Verkhratsky","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1080\/10408444.2020.1838441","article-title":"The aging brain, impact of heavy metal neurotoxicity","volume":"50","author":"Ijomone","year":"2020","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/S1474-4422(14)70117-6","article-title":"The role of iron in brain ageing and neurodegenerative disorders","volume":"13","author":"Ward","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fnagi.2014.00077","article-title":"The role of intracellular zinc release in aging, oxidative stress; and Alzheimer\u2019s disease","volume":"6","author":"McCord","year":"2014","journal-title":"Front. Aging Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.18632\/aging.101069","article-title":"Dissociation between iron accumulation and ferritin upregulation in the aged substantia nigra, attenuation by dietary restriction","volume":"8","author":"Walker","year":"2016","journal-title":"Aging"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s10522-006-9045-7","article-title":"Oxidative stress and brain aging, is zinc the link?","volume":"7","author":"Frazzini","year":"2006","journal-title":"Biogerontology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.mrfmmm.2003.08.004","article-title":"Labile iron pool, the main determinant of cellular response to oxidative stress","volume":"531","author":"Kruszewski","year":"2003","journal-title":"Mutat. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Choi, S., Hong, D.K., Choi, B.Y., and Suh, S.W. (2020). Zinc in the Brain, Friend or Foe?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21238941"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0361-9230(01)00452-X","article-title":"Roles of the metallothionein family of proteins in the central nervous system","volume":"55","author":"Hidalgo","year":"2001","journal-title":"Brain Res. Bull."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1002\/glia.23465","article-title":"Metallothionein-I\/II expression associates with the astrocyte DNA damage response and not Alzheimer-type pathology in the aging brain","volume":"66","author":"Waller","year":"2018","journal-title":"Glia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1007\/s00775-011-0799-2","article-title":"Chemistry and biology of mammalian metallothioneins","volume":"16","author":"Vasak","year":"2011","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1292\/jvms.60.351","article-title":"Localization of metallthionein-I and II in hypertrophic astrocytes in brain lesions of dogs","volume":"60","author":"Shimada","year":"1998","journal-title":"J. Vet. Med. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1292\/jvms.61.343","article-title":"Localization of Metallothioneins-\u2160& -\u2161 and \u2162 in the brain of aged dog","volume":"61","author":"Kojima","year":"1999","journal-title":"J. Vet. Med. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0361-9230(01)00468-3","article-title":"Zinc-bound metallothioneins as potential biological markers of ageing","volume":"55","author":"Mocchegiani","year":"2001","journal-title":"Brain Res. Bull."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jchemneu.2008.02.008","article-title":"Accumulation of copper and other metal ions; and metallothionein I\/II expression in the bovine brain as a function of aging","volume":"36","author":"Zatta","year":"2008","journal-title":"J. Chem. Neuroanat."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/BF02705235","article-title":"Age-related changes of structures in cerebellar cortex of cat","volume":"31","author":"Zhang","year":"2006","journal-title":"J. Biosci."},{"key":"ref_28","first-page":"540","article-title":"Age-related changes in cat brains as demonstrated by histological and immunohistochemical techniques","volume":"161","author":"Ozsoy","year":"2010","journal-title":"Revue Med. Vet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1159\/000065696","article-title":"Iron, a pathological mediator of Alzheimer disease?","volume":"24","author":"Bishop","year":"2002","journal-title":"Dev. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1098\/rsob.170228","article-title":"The role of astrocytes in amyloid production and Alzheimer\u2019s disease","volume":"7","author":"Frost","year":"2017","journal-title":"Open Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/BF03033779","article-title":"Metallothionein biology in the ageing and neurodegenerative brain","volume":"7","author":"Dittmann","year":"2005","journal-title":"Neurotox. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jfms.2009.12.006","article-title":"AAFP-AAHA Feline Life Stage Guidelines","volume":"12","author":"Vogt","year":"2010","journal-title":"J. Feline Med. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1679\/aohc.70.1","article-title":"Nonheme-iron histochemistry for light and electron microscopy, a historical; theoretical and technical review","volume":"70","author":"Meguro","year":"2007","journal-title":"Arch. Histol. Cytol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1134\/S0022093013030134","article-title":"Intranuclear localization of iron in neurons of mammalian brain","volume":"49","author":"Sukhorukova","year":"2013","journal-title":"J. Evol. Biochem. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"660022","DOI":"10.3389\/fvets.2021.660022","article-title":"Glial Fibrillary Acidic Protein and Ionized Calcium-Binding Adapter Molecule 1 Immunostaining Score for the Central Nervous System of Horses with Non-suppurative Encephalitis and Encephalopathies","volume":"8","author":"Boos","year":"2021","journal-title":"Front. Vet. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1292\/jvms.22-0386","article-title":"Different A\u03b243 deposition patterns in the brains of aged dogs, sea lions, and cats","volume":"84","author":"Takahashi","year":"2022","journal-title":"J. Vet. Med. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s12017-009-8102-1","article-title":"Metal ion physiopathology in neurodegenerative disorders","volume":"11","author":"Bolognin","year":"2009","journal-title":"Neuro. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jcpa.2005.01.001","article-title":"Immunohistochemical and ultrastructural findings related to the blood--brain barrier in the blood vessels of the cerebral white matter in aged dogs","volume":"133","author":"Morita","year":"2005","journal-title":"J. Comp. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.neulet.2005.03.003","article-title":"Ferrous and ferric iron accumulates in the brain of aged Long-Evans Cinnamon rats; an animal model of Wilson\u2019s disease","volume":"382","author":"Kim","year":"2005","journal-title":"Neurosci. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1679\/aohc.71.205","article-title":"Cellular and subcellular localizations of nonheme ferric and ferrous iron in the rat brain, a light and electron microscopic study by the perfusion-Perls and -Turnbull methods","volume":"71","author":"Meguro","year":"2008","journal-title":"Arch. Histol. Cytol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1369\/0022155413501325","article-title":"Comparison of histological techniques to visualize iron in paraffin-embedded brain tissue of patients with Alzheimer\u2019s disease","volume":"61","author":"Nabuurs","year":"2013","journal-title":"J. Histochem. Cytochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1016\/j.neurobiolaging.2015.05.022","article-title":"Activated iron-containing microglia in the human hippocampus identified by magnetic resonance imaging in Alzheimer disease","volume":"36","author":"Zeineh","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.3233\/JAD-161143","article-title":"Cortical Iron Reflects Severity of Alzheimer\u2019s Disease","volume":"60","author":"Bulk","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11724","DOI":"10.1038\/s41598-022-15812-4","article-title":"Activation of the Hepcidin-Ferroportin1 pathway in the brain and astrocytic-neuronal crosstalk to counteract iron dyshomeostasis during aging","volume":"12","author":"Mezzanotte","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1759091416670978","DOI":"10.1177\/1759091416670978","article-title":"Enhanced Histochemical Detection of Iron in Paraffin Sections of Mouse Central Nervous System Tissue, Application in the APP\/PS1 Mouse Model of Alzheimer\u2019s Disease","volume":"8","author":"Sands","year":"2016","journal-title":"ASN Neuro"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"12419","DOI":"10.1038\/s41598-021-91899-5","article-title":"In vivo multi-parametric manganese-enhanced MRI for detecting amyloid plaques in rodent models of Alzheimer\u2019s disease","volume":"11","author":"Kim","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e1198458","DOI":"10.1080\/21675511.2016.1198458","article-title":"Pathological relationships involving iron and myelin may constitute a shared mechanism linking various rare and common brain diseases","volume":"4","author":"Heidari","year":"2016","journal-title":"Rare Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.nimb.2007.02.069","article-title":"Intracellular iron concentration of neurons with and without perineuronal nets","volume":"260","author":"Fiedler","year":"2007","journal-title":"Nucl. Instrum. Methods Phys. Res. B Beam Interact. Mater. At."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Reinert, A., Morawski, M., Seeger, J., Arendt, T., and Reinert, T. (2019). Iron concentrations in neurons and glial cells with estimates on ferritin concentrations. BMC Neurosci., 20.","DOI":"10.1186\/s12868-019-0507-7"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3389\/fnagi.2017.00066","article-title":"Identification of Cerebral Metal Ion Imbalance in the Brain of Aging Octodon degus","volume":"9","author":"Braidy","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5213","DOI":"10.1007\/s12035-016-0067-0","article-title":"Expression of Iron Transporters and Pathological Hallmarks of Parkinson\u2019s and Alzheimer\u2019s Diseases in the Brain of Young, Adult, and Aged Rats","volume":"54","author":"Lu","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1385\/BTER:80:2:145","article-title":"Age-related changes in the concentrations of major and trace elements in the brain of rats and mice","volume":"80","author":"Takahashi","year":"2001","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/S0076-6879(02)48642-9","article-title":"Metallothionein expression and oxidative stress in the brain","volume":"Volume 348","author":"Hidalgo","year":"2002","journal-title":"Methods in Enzymology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.neuro.2007.12.006","article-title":"Metallothionein in the central nervous system: Roles in protection, regeneration and cognition","volume":"29","author":"West","year":"2008","journal-title":"Neurotoxicology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1267\/ahc.25.609","article-title":"Localization of metallothionein in the brain of Macaca fascicularis","volume":"25","author":"Suzuki","year":"1992","journal-title":"Acta Histochem. Cytochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1177\/40.2.1552172","article-title":"Localization of metallothionein in the brain of rat and mouse","volume":"40","author":"Nishimura","year":"1992","journal-title":"J. Histochem. Cytochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1002\/glia.440040607","article-title":"Glial immunoreactivity for metallothionein in the rat brain","volume":"4","author":"Young","year":"1991","journal-title":"Glia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5844","DOI":"10.1523\/JNEUROSCI.14-10-05844.1994","article-title":"Metallothionein III is expressed in neurons that sequester zinc in synaptic vesicles","volume":"14","author":"Masters","year":"1994","journal-title":"J. Neurosci."},{"key":"ref_59","first-page":"725","article-title":"Immunohistochemical investigation of amyloid beta-protein (Abeta) in the brain of aged cats","volume":"20","author":"Brellou","year":"2005","journal-title":"Histol. Histopathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.neurobiolaging.2004.06.015","article-title":"Beta-amyloid deposition and tau phosphorylation in clinically characterized aged cats","volume":"26","author":"Head","year":"2005","journal-title":"Neurobiol. Aging."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.jfms.2006.01.003","article-title":"Ageing changes in cat brains demonstrated by beta-amyloid and AT8-immunoreactive phosphorylated tau deposits","volume":"8","author":"McVee","year":"2006","journal-title":"J. Feline Med. Surg."},{"key":"ref_62","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_63","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1212\/WNL.58.12.1791","article-title":"Phases of A beta-deposition in the human brain and its relevance for the development of AD","volume":"58","author":"Thal","year":"2002","journal-title":"Neurology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/j.1471-4159.2004.02857.x","article-title":"Alzheimer\u2019s disease beta-secretase BACE1 is not a neuron-specific enzyme","volume":"92","author":"Rossner","year":"2005","journal-title":"J. Neurochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1159\/000083496","article-title":"Neuronal and nonneuronal quantitative BACE immunocytochemical expression in the entorhinohippocampal and frontal regions in Alzheimer\u2019s disease","volume":"19","author":"Leuba","year":"2005","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.bbrc.2012.07.123","article-title":"Ab-induced Ca2\u03ce influx regulates astrocytic BACE1 expression via calcineurin\/NFAT4 signals","volume":"425","author":"Jin","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1016\/j.neurobiolaging.2014.06.004","article-title":"Isolation of glia from Alzheimer\u2019s mice reveals inflammation and dysfunction","volume":"35","author":"Orre","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/1742-2094-8-150","article-title":"The contribution of activated astrocytes to Ab production, implications for Alzheimer\u2019s disease pathogenesis","volume":"8","author":"Zhao","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1006\/nbdi.2000.0321","article-title":"Costimulatory effects of interferon-g and interleukin-1b or tumor necrosis factor a on the synthesis of Ab1\u201340 and Ab1\u201342 by human astrocytes","volume":"7","author":"Blasko","year":"2000","journal-title":"Neurobiol. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1354\/vp.36-3-202","article-title":"Age related changes in the brain of the dog","volume":"36","author":"Borras","year":"1999","journal-title":"Vet. Pathol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1053\/jcpa.2000.0428","article-title":"Histological observations on the brains of symptomless 7-year-old cattle","volume":"124","author":"Wells","year":"2001","journal-title":"J. Comp. Pathol."},{"key":"ref_72","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_73","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.neuroimage.2010.11.073","article-title":"Increased brain iron coincides with early plaque formation in a mouse model of Alzheimer\u2019s disease","volume":"55","author":"Leskovjan","year":"2011","journal-title":"Neuroimage"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/13\/7\/1115\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:17:15Z","timestamp":1760127435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/13\/7\/1115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,22]]},"references-count":73,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["brainsci13071115"],"URL":"https:\/\/doi.org\/10.3390\/brainsci13071115","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,22]]}}}