{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:27:42Z","timestamp":1793834862267,"version":"4.6.1"},"reference-count":103,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH\/NCCIH","doi-asserted-by":"publisher","award":["5R33AT010637-01A1"],"award-info":[{"award-number":["5R33AT010637-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH\/NCCIH","doi-asserted-by":"publisher","award":["3R33 AT010637-02S1"],"award-info":[{"award-number":["3R33 AT010637-02S1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Malcolm Feist Endowed Chair in Diabetes"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disorder marked by amyloid-\u03b2 buildup, tau pathology, neuroinflammation, and declining cognition. Adiponectin, a hormone produced by adipose tissue with insulin-sensitizing, anti-inflammatory, and antioxidant effects, may link peripheral metabolic health to brain function. Studies show that adiponectin helps neurons survive, improves synaptic plasticity, maintains blood\u2013brain barrier integrity, and reduces amyloid-\u03b2 and tau damage via AdipoR1\/R2 signaling. Clinical studies evaluating circulating adiponectin have yielded inconsistent findings, giving rise to the \u2018adiponectin paradox\u2019 whereby elevated adiponectin levels in older adults and patients with AD may reflect frailty, weight loss, systemic inflammation, or compensatory responses rather than direct neuroprotective effects. Studies indicate that vitamin D (VD) and L-cysteine (L-Cys), a precursor to glutathione, act synergistically to modulate oxidative stress, inflammation, and adiponectin levels. VD increases circulating adiponectin and benefits metabolism, while L-Cys boosts glutathione, restores redox balance, and promotes adiponectin secretion by affecting fat cell function. Emerging experimental evidence, together with clinical observations from metabolic disorders, suggests that VD and L-Cys may influence adiponectin-related pathways, oxidative stress, and inflammation, which are implicated in AD pathogenesis. However, direct clinical evidence demonstrating that combined VD and L-Cys supplementation modulates these pathways or alters AD progression in humans is currently lacking. This narrative review covers current knowledge of adiponectin and its links to obesity, metabolic issues, and AD, and it also explores the roles of VD and L-Cys as regulators of adiponectin signaling. Overall, the available evidence supports the proposed interaction among VD\u2013L-Cys and adiponectin, which warrants further mechanistic investigation and well-designed clinical studies to determine its therapeutic relevance in AD.<\/jats:p>","DOI":"10.3390\/nu18152440","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:49:27Z","timestamp":1785131367000},"page":"2440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Vitamin D and L-Cysteine as Potential Regulators of Adiponectin in Alzheimer\u2019s Disease: A Narrative Review"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7905-1887","authenticated-orcid":false,"given":"Jeffrey","family":"Justin Margret","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Louisiana State University Health Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushil K.","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Louisiana State University Health Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","article-title":"The neuropathological diagnosis of Alzheimer\u2019s disease","volume":"14","author":"DeTure","year":"2019","journal-title":"Mol. 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