{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T23:15:02Z","timestamp":1784243702902,"version":"3.55.0"},"reference-count":87,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000320","name":"Alzheimer\u2019s Society","doi-asserted-by":"publisher","award":["AS-PhD-18-007"],"award-info":[{"award-number":["AS-PhD-18-007"]}],"id":[{"id":"10.13039\/501100000320","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Accumulation of hyper-phosphorylated tau and amyloid beta (A\u03b2) are key pathological hallmarks of Alzheimer\u2019s disease (AD). Increasing evidence indicates that in the early pre-clinical stages of AD, phosphorylation and build-up of tau drives impairments in hippocampal excitatory synaptic function, which ultimately leads to cognitive deficits. Consequently, limiting tau-related synaptic abnormalities may have beneficial effects in AD. There is now significant evidence that the hippocampus is an important brain target for the endocrine hormone leptin and that leptin has pro-cognitive properties, as activation of synaptic leptin receptors markedly influences higher cognitive processes including learning and memory. Clinical studies have identified a link between the circulating leptin levels and the risk of AD, such that AD risk is elevated when leptin levels fall outwith the physiological range. This has fuelled interest in targeting the leptin system therapeutically. Accumulating evidence supports this possibility, as numerous studies have shown that leptin has protective effects in a variety of models of AD. Recent findings have demonstrated that leptin has beneficial effects in the preclinical stages of AD, as leptin prevents the early synaptic impairments driven by tau protein and amyloid \u03b2. Here we review recent findings that implicate the leptin system as a potential novel therapeutic target in AD.<\/jats:p>","DOI":"10.3390\/ijms25137352","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T12:21:03Z","timestamp":1720441263000},"page":"7352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Novel Leptin-Based Therapeutic Strategies to Limit Synaptic Dysfunction in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9858-001X","authenticated-orcid":false,"given":"Jenni","family":"Harvey","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19393","DOI":"10.1038\/srep19393","article-title":"Extra-cellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory","volume":"6","author":"Puzzo","year":"2016","journal-title":"Sci. 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