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Here, we investigate proteasome function and localization at synapses in Alzheimer\u2019s disease (AD)\n                    <jats:italic>post-mortem<\/jats:italic>\n                    brain tissue and in experimental models. We found a marked increase in ubiquitinylated proteins in\n                    <jats:italic>post-mortem<\/jats:italic>\n                    AD hippocampi compared to controls. Using several experimental models, we show that amyloid-\u03b2 oligomers (A\u03b2Os) inhibit synaptic proteasome activity and trigger a reduction in synaptic proteasome content. We further show proteasome inhibition specifically in hippocampal synaptic fractions derived from APPswePS1\u0394E9 mice. Reduced synaptic proteasome activity instigated by A\u03b2Os is corrected by treatment with rolipram, a phosphodiesterase-4 inhibitor, in mice. Results further show that dynein inhibition blocks A\u03b2O-induced reduction in dendritic proteasome content in hippocampal neurons. Finally, proteasome inhibition induces AD-like pathological features, including reactive oxygen species and dendritic spine loss in hippocampal neurons, inhibition of hippocampal mRNA translation, and memory impairment in mice. Results suggest that proteasome inhibition may contribute to synaptic and memory deficits in AD.\n                  <\/jats:p>","DOI":"10.1038\/s42003-023-05511-9","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T09:01:35Z","timestamp":1699347695000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Synaptic proteasome is inhibited in Alzheimer\u2019s disease models and associates with memory impairment in mice"],"prefix":"10.1038","volume":"6","author":[{"given":"Felipe C.","family":"Ribeiro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Cozachenco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana","family":"Heimfarth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6943-0872","authenticated-orcid":false,"given":"Juliana T. 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