{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:01:32Z","timestamp":1790017292604,"version":"4.0.1"},"reference-count":61,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,2,14]]},"abstract":"<jats:p>Background: Mitochondrial (MT) dysfunction is a hallmark of Alzheimer\u2019s disease (AD). Amyloid-\u03b2 protein precursor and amyloid-\u03b2 peptides localize to MT and lead to MT dysfunction in familial forms of AD. This dysfunction may trigger subsequent types of pathology. Objective: To identify the MT phenotypes that occur early in order to help understand the cascade of AD pathophysiology. Methods: The 5xFAD mouse model was used to explore the time course of MT pathologies in both sexes. Protein biomarkers for MT dynamics were measured biochemically and MT function was measured using oxygen consumption and ATP assays. Results: We discovered progressive alterations in mitochondrial dynamics (biogenesis, fission, fusion, and mitophagy) and function (O2 consumption, ATP generation, and Ca2+ import) in the hippocampus of 5xFAD mice in both sexes as early as 2 months of age. Thus, mitochondrial dynamics and function become altered at young ages, consistent with an early role for mitochondria in the AD pathological cascade. Conclusion: Our study offers the baseline information required to understand the hierarchical relationship between the multiple pathologies that develop in this mouse model and provides early biomarkers for MT dysfunction. This will aid in dissecting the temporal cascade of pathologies, understanding sex-specific differences, and in testing the efficacy of putative mitochondrial therapeutics.<\/jats:p>","DOI":"10.3233\/jad-220884","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T14:20:53Z","timestamp":1672755653000},"page":"1323-1338","source":"Crossref","is-referenced-by-count":20,"title":["Early Mitochondrial Defects in the 5xFAD Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"91","author":[{"given":"Neelam","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Florida Scripps Biomedical Research Institute, Jupiter, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupkatha","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Florida Scripps Biomedical Research Institute, Jupiter, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald L.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Florida Scripps Biomedical Research Institute, Jupiter, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-220884_ref1","doi-asserted-by":"crossref","first-page":"77sr71","DOI":"10.1126\/scitranslmed.3002369","article-title":"Alzheimer\u2019s disease: The challenge of the second century","volume":"3","author":"Holtzman","year":"2011","journal-title":"Sci Transl Med"},{"key":"10.3233\/JAD-220884_ref2","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1038\/s41593-018-0237-7","article-title":"Converging pathways in neurodegeneration, from genetics to mechanisms","volume":"21","author":"Gan","year":"2018","journal-title":"Nat 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