{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:16:54Z","timestamp":1791487014307,"version":"4.3.4"},"reference-count":213,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Khalid University","award":["RGP2\/179\/46"],"award-info":[{"award-number":["RGP2\/179\/46"]}]},{"name":"Shaqra University","award":["RGP2\/179\/46"],"award-info":[{"award-number":["RGP2\/179\/46"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Aging is a key risk factor for neurodegenerative disorders and is associated with widespread systemic and brain-specific changes. Alzheimer\u2019s disease (AD), a progressive and irreversible brain disorder, primarily affects older adults and leads to a gradual decline in cognitive function. The underlying disease mechanisms often begin years before clinical symptoms appear, limiting the effectiveness of current treatments. Several factors linked to aging\u2014including inflammation, oxidative stress, impaired metabolism, and protein aggregation\u2014contribute to the onset and progression of AD. A central feature of AD is the abnormal accumulation of amyloid beta (A\u03b2) and tau, a microtubule-associated protein, driven by post-translational modifications such as acetylation and hyperphosphorylation. These modifications lead to structural changes in tau, promoting the formation of neurofibrillary tangles (NFTs), which are more closely associated with cognitive decline than A\u03b2 plaques. Interestingly, tau accumulation and the resulting cognitive impairments are often observed in aged individuals without A\u03b2 deposition, highlighting tauopathy as a distinct contributor to age-related cognitive decline. This review focuses on new developments in therapeutic approaches that target oxidative stress, protein aggregation, and neuroinflammation, and our current understanding of the molecular pathways relating aging and tau pathology in AD.<\/jats:p>","DOI":"10.3390\/antiox14070774","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T09:24:18Z","timestamp":1750757058000},"page":"774","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Interplay Between Aging and Tau Pathology in Alzheimer\u2019s Disease: Mechanisms and Translational Perspectives"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9645-0572","authenticated-orcid":false,"given":"Mohammed","family":"Alrouji","sequence":"first","affiliation":[{"name":"Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra 11961, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed S.","family":"Alshammari","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Shaqra 11961, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5253-7606","authenticated-orcid":false,"given":"Syed","family":"Tasqeeruddin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha 62521, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7055-7056","authenticated-orcid":false,"given":"Anas","family":"Shamsi","sequence":"additional","affiliation":[{"name":"Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman P.O. Box 346, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, May 25). Dementia. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/dementia."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a risk factor for neurodegenerative disease","volume":"15","author":"Hou","year":"2019","journal-title":"Nat. Rev. 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