{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T21:40:18Z","timestamp":1785879618084,"version":"3.56.0"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000320","name":"Alzheimer's Society","doi-asserted-by":"publisher","award":["AS\u2010PhD\u201018\u2010007"],"award-info":[{"award-number":["AS\u2010PhD\u201018\u2010007"]}],"id":[{"id":"10.13039\/501100000320","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Amyloid\u2010\u03b2 (A\u03b2) and hyper\u2010phosphorylated tau are key hallmarks of Alzheimer's disease (AD), with an accumulation of both proteins linked to hippocampal synaptic dysfunction. Recent evidence indicates that A\u03b2 drives mis\u2010localisation of tau from axons to synapses, resulting in AMPA receptor (AMPAR) internalisation and impaired excitatory synaptic function. These tau\u2010driven synaptic impairments are thought to underlie the cognitive deficits in AD. Consequently, limiting the synapto\u2010toxic effects of tau may prevent AD\u2010related cognitive deficits. Increasing evidence links leptin dysfunction with higher AD risk, and numerous studies have identified neuroprotective properties of leptin in AD models of A\u03b2\u2010induced toxicity. However, it is unclear if leptin protects against tau\u2010related synaptic dysfunction. Here we show that A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    significantly increases dendritic and synaptic levels of tau and p\u2010tau in hippocampal neurons, and these effects were blocked by leptin. In accordance with GSK\u20103\u03b2 being involved in tau phosphorylation, the protective effects of leptin involve PI 3\u2010kinase (PI3K) activation and inhibition of GSK\u20103\u03b2. A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    \u2010driven synaptic targeting of tau was associated with the removal of GluA1\u2010containing AMPARs from synapses, which was also inhibited by leptin\u2010driven inhibition of GSK\u20103\u03b2. Direct application of oligomeric tau to hippocampal neurons caused internalisation of GluA1\u2010containing AMPARs and this effect was blocked by prior application of leptin. Similarly, leptin prevented the ability of tau to block induction of activity\u2010dependent long\u2010term potentiation (LTP) at hippocampal SC\u2010CA1 synapses. These findings increase our understanding of the neuroprotective actions of leptin in the early pre\u2010clinical stages of AD and further validate the leptin system as a therapeutic target in AD.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15980-fig-0007-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.15980","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T03:05:50Z","timestamp":1697079950000},"page":"520-537","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Leptin prevents aberrant targeting of tau to hippocampal synapses via\n                    <scp>PI<\/scp>\n                    3 kinase driven inhibition of\n                    <scp>GSK3\u03b2<\/scp>"],"prefix":"10.1111","volume":"167","author":[{"given":"Kirsty","family":"Hamilton","sequence":"first","affiliation":[{"name":"Division of Systems Medicine, Ninewells Hospital and Medical School University of Dundee  Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Morrow","sequence":"additional","affiliation":[{"name":"Division of Systems Medicine, Ninewells Hospital and Medical School University of Dundee  Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ermione","family":"Markantoni","sequence":"additional","affiliation":[{"name":"Division of Systems Medicine, Ninewells Hospital and Medical School University of Dundee  Dundee 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