{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T05:59:18Z","timestamp":1793771958737,"version":"4.6.1"},"reference-count":143,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2024,4,16]]},"abstract":"<jats:p>Animal models, particularly transgenic mice, are extensively used in Alzheimer\u2019s disease (AD) research to emulate key disease hallmarks, such as amyloid plaques and neurofibrillary tangles formation. Although these models have contributed to our understanding of AD pathogenesis and can be helpful in testing potential therapeutic interventions, their reliability is dubious. While preclinical studies have shown promise, clinical trials often yield disappointing results, highlighting a notable gap and disparity between animal models and human AD pathology. Existing models frequently overlook early-stage human pathologies and other key AD characteristics, thereby limiting their application in identifying optimal therapeutic interventions. Enhancing model reliability necessitates rigorous study design, comprehensive behavioral evaluations, and biomarker utilization. Overall, a nuanced understanding of each model\u2019s neuropathology, its fidelity to human AD, and its limitations is essential for accurate interpretation and successful translation of findings. This article analyzes the discrepancies between animal models and human AD pathology that complicate the translation of findings from preclinical studies to clinical applications. We also delve into AD pathogenesis and attributes to propose a new perspective on this pathology and deliberate over the primary limitations of key experimental models. Additionally, we discuss several fundamental problems that may explain the translational failures and suggest some possible directions for more effective preclinical studies.<\/jats:p>","DOI":"10.3233\/jad-240058","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T12:07:03Z","timestamp":1710850023000},"page":"1199-1218","source":"Crossref","is-referenced-by-count":46,"title":["Addressing the Discrepancies Between Animal Models and Human Alzheimer\u2019s Disease Pathology: Implications for Translational Research"],"prefix":"10.1177","volume":"98","author":[{"given":"Baruh","family":"Polis","sequence":"first","affiliation":[{"name":"Bar-Ilan University Azrieli Faculty of Medicine, Safed, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham O.","family":"Samson","sequence":"additional","affiliation":[{"name":"Bar-Ilan University Azrieli Faculty of Medicine, Safed, 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Neurol"},{"key":"10.3233\/JAD-240058_ref39","doi-asserted-by":"crossref","first-page":"4063","DOI":"10.2174\/1381612822666160518142110","article-title":"Non-demented individuals with Alzheimer\u2019s disease neuropathology: Resistance to cognitive decline may reveal new treatment strategies","volume":"22","author":"Zolochevska","year":"2016","journal-title":"Curr Pharm Des"},{"key":"10.3233\/JAD-240058_ref40","doi-asserted-by":"crossref","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":"10.3233\/JAD-240058_ref41","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1126\/science.1566067","article-title":"Alzheimer\u2019s disease: The amyloid cascade 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Neurochem"},{"key":"10.3233\/JAD-240058_ref51","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.jalz.2010.08.228","article-title":"Intracranial atherosclerosis as a contributing factor to Alzheimer\u2019s disease dementia","volume":"7","author":"Roher","year":"2011","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-240058_ref52","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00401-006-0136-y","article-title":"Circle of Willis atherosclerosis: Association with Alzheimer\u2019s disease, neuritic plaques and neurofibrillary tangles","volume":"113","author":"Beach","year":"2007","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-240058_ref53","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1212\/01.WNL.0000150886.50187.30","article-title":"Atherosclerosis and AD: Analysis of data from the US National Alzheimer\u2019s Coordinating 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system","volume":"101","author":"Binder","year":"1985","journal-title":"J Cell Biol"},{"key":"10.3233\/JAD-240058_ref57","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/ana.410410106","article-title":"Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer\u2019s disease","volume":"41","author":"Gomez-Isla","year":"1997","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-240058_ref58","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1136\/jnnp.2003.021295","article-title":"Frontotemporal dementia: Impact of P301L tau mutation on a healthy carrier","volume":"75","author":"Alberici","year":"2004","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.3233\/JAD-240058_ref59","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/78078","article-title":"Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau 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