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Its dysfunction may precede Alzheimer\u2019s disease (AD) hallmarks. Here we evaluated the effects of a synthetic single-stranded cDNA (APT20TTMG) that interacts with U1 snRNP, in iPSC-derived neurons from a donor diagnosed with AD and in the SAMP8 mouse model. APT20TTMG effectively binds to U1 snRNP, specifically decreasing TAU in AD neurons, without changing mitochondrial activity or glutamate. Treatment enhanced neuronal electrical activity, promoted an enrichment of differentially expressed genes related to key processes affected by AD. In SAMP8 mice, APT20TTMG reduced insoluble pTAU in the hippocampus, amyloid-beta and GFAP in the cortex, and U1-70\u00a0K in both brain regions, without cognitive changes. This study highlights the correction of the U1 snRNP complex as a new target for AD.<\/jats:p>","DOI":"10.1038\/s41598-024-81687-2","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T11:46:49Z","timestamp":1733226409000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effects of the therapeutic correction of U1 snRNP complex on Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"14","author":[{"given":"Caio Bruno Q. S.","family":"Leal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila G. M.","family":"Zimmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa V. 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