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There is also new evidence of a high correlation between obesity and a higher risk of neurodegenerative diseases, including Alzheimer's disease (AD). This review provides a systematic discussion of the dysregulation of two major adipokines\u2014leptin and adiponectin\u2014and their possible involvement in the development of Alzheimer's. We collected and critically reviewed outcomes of in\u00a0vitro studies, in\u00a0vivo animal models and clinical studies of the altered signaling effects of leptin and adiponectin in the central nervous system, with an emphasis on the effects of this altered signaling on synaptic plasticity, neuronal survival, A\u03b2 accumulation, and tau pathology. Leptin has a cardinal role in the brain that protects from neurogenesis, synaptic plasticity, and neuronal survival and is dysregulated by increased amyloid\u2010beta accumulation and tau hyperphosphorylation. Adiponectin, the most abundant circulating adipokine, has anti\u2010inflammatory and insulin\u2010sensitizing effects, and deficiency is associated with impaired neurogenesis, neuronal insulin resistance and worsening of AD pathological hallmarks. The pathogenesis of AD may significantly be attributed to the dysregulation of leptin and adiponectin. Pathways aimed at adipokine signaling appear as a promising entry point for therapeutic intervention in trying to reduce or delay the development of AD in an obese and at\u2010risk population.<\/jats:p>","DOI":"10.1111\/ejn.70326","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T02:17:20Z","timestamp":1762913840000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Role of Leptin and Adiponectin in the Management of Alzheimer's Disease: A Systematic Review"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0149-7349","authenticated-orcid":false,"given":"Manal","family":"Adil","sequence":"first","affiliation":[{"name":"Department of Pathology Green International University  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiza","family":"Ghulammohiuddin","sequence":"additional","affiliation":[{"name":"Department 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