{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:37:48Z","timestamp":1790473068183,"version":"4.1.0"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"2","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,1,13]]},"abstract":"<jats:p>\n            Synapse loss strongly correlates with cognitive decline in Alzheimer\u2019s disease (AD), but the underlying mechanisms are poorly understood. Deficient Wnt signaling contributes to synapse dysfunction and loss in AD. Consistently, a variant of the\n            <jats:italic>LRP6<\/jats:italic>\n            receptor, (\n            <jats:italic>LRP6-Val<\/jats:italic>\n            ), with reduced Wnt signaling, is linked to late-onset AD. However, the impact of\n            <jats:italic>LRP6-Val<\/jats:italic>\n            on the healthy and AD brain has not been examined. Knock-in mice, generated by gene editing, carrying this\n            <jats:italic>Lrp6<\/jats:italic>\n            variant develop normally. However, neurons from\n            <jats:italic>Lrp6-val<\/jats:italic>\n            mice do not respond to Wnt7a, a ligand that promotes synaptic assembly through the Frizzled-5 receptor. Wnt7a stimulates the formation of the low-density lipoprotein receptor-related protein 6 (LRP6)\u2013Frizzled-5 complex but not if LRP6-Val is present.\n            <jats:italic>Lrp6-val<\/jats:italic>\n            mice exhibit structural and functional synaptic defects that become pronounced with age.\n            <jats:italic>Lrp6-val<\/jats:italic>\n            mice present exacerbated synapse loss around plaques when crossed to the\n            <jats:italic>NL-G-F<\/jats:italic>\n            AD model. Our findings uncover a previously unidentified role for\n            <jats:italic>Lrp6-val<\/jats:italic>\n            in synapse vulnerability during aging and AD.\n          <\/jats:p>","DOI":"10.1126\/sciadv.abo7421","type":"journal-article","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T18:59:11Z","timestamp":1673636351000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":36,"title":["A genetic variant of the Wnt receptor LRP6 accelerates synapse degeneration during aging and in Alzheimer\u2019s disease"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8056-2016","authenticated-orcid":true,"given":"Megan E.","family":"Jones","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology, University College London, London WC1E 6BT, 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