{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:24:25Z","timestamp":1791296665559,"version":"4.1.0"},"reference-count":147,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bosch i Gimpera Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human brain aging is characterized by the production and deposition of \u03b2-amyloid (A\u03b2) in the form of senile plaques and cerebral amyloid angiopathy and the intracellular accumulation of hyper-phosphorylated tau (Hp-tau) to form neurofibrillary tangles (NFTs) and dystrophic neurites of senile plaques. The process progresses for years and eventually manifests as cognitive impairment and dementia in a subgroup of aged individuals. A\u03b2 is produced and deposited first in the neocortex in most aged mammals, including humans; it is usually not accompanied by altered behavior and cognitive impairment. Hp-tau is less frequent than A\u03b2 pathology, and NFTs are rare in most mammals. In contrast, NFTs are familiar from middle age onward in humans; NFTs first appear in the paleocortex and selected brain stem nuclei. NFTs precede for decades or years A\u03b2 deposition and correlate with dementia in about 5% of individuals at the age of 65 and 25% at the age of 85. Based on these comparative data, (a) A\u03b2 deposition is the most common Alzheimer\u2019s disease neuropathological change (ADNC) in the brain of aged mammals; (b) Hp-tau is less common, and NFTs are rare in most aged mammals; however, NFTs are the principal cytoskeletal pathology in aged humans; (c) NFT in aged humans starts in selected nuclei of the brain stem and paleocortical brain regions progressing to the most parts of the neocortex and other regions of the telencephalon; (d) human brain aging is unique among mammalian species due to the early appearance and dramatic progression of NFTs from middle age onward, matching with cognitive impairment and dementia in advanced cases; (e) neither mammalian nor human brain aging supports the concept of the amyloid cascade hypothesis.<\/jats:p>","DOI":"10.3390\/ijms25158118","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T11:43:44Z","timestamp":1721907824000},"page":"8118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Alzheimer\u2019s Disease Neuropathological Change in Aged Non-Primate Mammals"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-8754","authenticated-orcid":false,"given":"Isidro","family":"Ferrer","sequence":"first","affiliation":[{"name":"Department of Pathology and Experimental Therapeutics, University of Barcelona, carrer Feixa Llarga sn, 08907 Hospitalet de Llobregat, Spain"},{"name":"Reial Acad\u00e8mia de Medicina de Catalunya, carrer del Carme 47, 08001 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"ref_1","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. 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