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Though people with Down syndrome (DS) are at markedly increased risk for AD (AD\u2010DS), few studies have addressed synapse dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Synaptic proteins were measured in the frontal cortex of DS, AD\u2010DS, sporadic AD cases, and controls. The same proteins were examined in the Dp16 model of DS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A common subset of synaptic proteins were reduced in AD and AD\u2010DS, but not in DS or a case of partial trisomy 21 lacking triplication of <jats:italic>APP<\/jats:italic> gene. Pointing to compromised synaptic function, the reductions in AD and AD\u2010DS were correlated with reduced SNARE complexes. In Dp16 mice reductions in syntaxin 1A, SNAP25 and the SNARE complex recapitulated findings in AD\u2010DS; reductions were impacted by both age and increased <jats:italic>App<\/jats:italic> gene dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Synaptic phenotypes shared between AD\u2010DS and AD point to shared pathogenetic mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.12835","type":"journal-article","created":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T10:14:19Z","timestamp":1668248059000},"page":"2095-2116","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Reduced synaptic proteins and SNARE complexes in Down syndrome with Alzheimer's disease and the Dp16 mouse Down syndrome model: Impact of <i>APP<\/i> gene dose"],"prefix":"10.1002","volume":"19","author":[{"given":"Xu\u2010Qiao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of 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