{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T20:16:57Z","timestamp":1788898617799,"version":"build-2803163510"},"reference-count":292,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32 HL007446-41"],"award-info":[{"award-number":["T32 HL007446-41"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017483","name":"Harry S. Moss Heart Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017483","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most common neurodegenerative disorder and a leading cause of dementia worldwide, characterized by progressive cognitive decline, memory impairment, and neuronal loss. The pathological hallmarks of AD include extracellular accumulation of amyloid-\u03b2 (A\u03b2) plaques, intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein, chronic neuroinflammation, oxidative stress, mitochondrial dysfunction, and synaptic degeneration. Current symptomatic therapies provide modest clinical benefits, while recently approved amyloid-targeting monoclonal antibodies, such as lecanemab and donanemab, can slow decline in selected early-stage AD patients but do not cure the disease and are associated with safety, access, and cost concerns. This narrative review summarizes mechanistic evidence from in vitro and in vivo studies and distinguishes preclinical promise from validated clinical utility. Phytochemicals, including polyphenols, flavonoids, alkaloids, terpenoids, and carotenoids, demonstrate neuroprotective effects through antioxidant activity, anti-inflammatory modulation, inhibition of amyloid aggregation, regulation of tau phosphorylation, and support of mitochondria and synapses. Evidence from experimental models suggests that several phytochemicals may help slow AD pathology and improve cognitive function, but clinical translation remains limited due to poor bioavailability, inadequate blood\u2013brain barrier (BBB) penetration, and a lack of large-scale clinical trials. This review highlights critical research gaps and emerging strategies to facilitate phytochemical-based preventive and therapeutic approaches in AD.<\/jats:p>","DOI":"10.3390\/ijms27146329","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:12:38Z","timestamp":1784257958000},"page":"6329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Phytochemicals in Alzheimer\u2019s Disease Prevention and Management: Molecular Mechanisms, Therapeutic Potential, Translational Challenges, and Emerging Research Directions"],"prefix":"10.3390","volume":"27","author":[{"given":"Muhammad Sohail","family":"Khan","sequence":"first","affiliation":[{"name":"College of Korean Medicine, Gachon University, 1342 Seongnamdaero, Seongnam 13120, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9246-0850","authenticated-orcid":false,"given":"Imran","family":"Zafar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, The University of Faisalabad (TUF), Faisalabad 38000, Punjab, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3667-5790","authenticated-orcid":false,"given":"Jean C.","family":"Bopassa","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, School of Medicine, University of Texas Health Science Center at San Antonio (UTHSCSA), 7703 Floyd Curl Dr., San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Abubakar, M.B., Sanusi, K.O., Ugusman, A., Mohamed, W., Kamal, H., Ibrahim, N.H., Khoo, C.S., and Kumar, J. 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