{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:57:03Z","timestamp":1788375423253,"version":"build-2803163510"},"reference-count":101,"publisher":"SAGE Publications","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,8,2]]},"abstract":"<jats:p>Background: Sporadic or late onset Alzheimer\u2019s disease (LOAD) is a multifactorial neurodegenerative disease with aging the most known risk factor. Non-human primates (NHPs) may serve as an excellent model to study LOAD because of their close similarity to humans in many aspects including neuroanatomy and neurodevelopment. Recent studies reveal AD-like pathology in old NHPs. Objective: In this pilot study, we took advantage of brain samples from 6 Cynomolgus macaques that were divided into two groups: middle aged (average age 14.81 years) and older (average age 19.33 years). We investigated whether AD-like brain pathologies are present in the NHPs. Methods: We used immunohistochemical method to examine brain A\u03b2 pathology and neuron density. We applied biochemical assays to measure tau phosphorylation and multiple signaling pathways indicated in AD. We performed electron microscopy experiments to study alterations of postsynaptic density and mitochondrial morphology in the brain of NHPs. Results: We found multiple AD-like pathological alteration in the prefrontal cortex (but not in the hippocampus) of the older NHPs including tau hyperphosphorylation, increased activity of AMP-activated protein kinase (AMPK), decreased expression of protein phosphatase 2A (PP2A), impairments in mitochondrial morphology, and postsynaptic densities formation. Conclusion: These findings may provide insights into the factors contributing to the development of LOAD, particularly during the early stage transitioning from middle to old age. Future endeavors are warranted to elucidate mechanisms underlying the regional (and perhaps cellular) vulnerability with aging and the functional correlation of such pathological changes in NHPs.<\/jats:p>","DOI":"10.3233\/jad-215303","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T13:13:37Z","timestamp":1655212417000},"page":"957-970","source":"Crossref","is-referenced-by-count":13,"title":["Characterization of Early Alzheimer\u2019s Disease-Like Pathological Alterations in Non-Human Primates with Aging: A Pilot Study"],"prefix":"10.1177","volume":"88","author":[{"given":"Hannah M.","family":"Jester","sequence":"first","affiliation":[{"name":"Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saahj P.","family":"Gosrani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiping","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Chuan","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, 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