{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:04Z","timestamp":1785437944903,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,5]]},"group-title":"Neuroscience","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["K08NS128239"],"award-info":[{"award-number":["K08NS128239"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30AG10161"],"award-info":[{"award-number":["P30AG10161"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30AG72975"],"award-info":[{"award-number":["P30AG72975"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AG17917"],"award-info":[{"award-number":["R01AG17917"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AG015819"],"award-info":[{"award-number":["R01AG015819"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U01AG072572"],"award-info":[{"award-number":["U01AG072572"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/02qenvm24","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Davis Alzheimer Prevention Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Missplicing due to U1 small nuclear ribonucleoprotein (U1 snRNP) insolubilization and dysfunction has been identified in Alzheimer disease (AD) brain. Cytoplasmic aggregation and mislocalization of the U1 snRNP partly co-localizes with tau neurofibrillary tangles, and some evidence for tau-U1 binding has been identified. However, tau-U1 co-localization by immunohistochemistry is only partial, and insoluble U1 small nuclear RNA (snRNA) binding proteins correlate better with A\u03b2 than with tau in unbiased proteomics. While investigating the sedimentation characteristics of A\u03b2 aggregates capable of diffusing out of AD brain tissue, we unexpectedly found that some were bound to small RNA. A\u03b2 immunoprecipitation and deep sequencing revealed the U1 snRNA, with specific binding confirmed through reverse immunoprecipitation and oligonucleotide hybridization. Double immunoelectron microscopy revealed decoration of A\u03b2 fibrils, more than tau fibrils, with the U1-70k protein, a component of the U1 snRNP. Immunofluorescence of unfixed cryostat sections but not formalin fixed paraffin embedded sections of AD brain revealed labeling of a subset of amyloid plaques with anti-U1-70k antibodies, confirmed by RNA\n                  <jats:italic>in situ<\/jats:italic>\n                  hybridization of the U1 snRNA. We conclude that a subset of AD brain A\u03b2 aggregates are bound to the U1 snRNP at the edges of some amyloid plaques, explaining prior proteomics findings. These data provide a potential link between A\u03b2 aggregation and spliceosome dysfunction and unite A\u03b2 with other fibril-forming proteins across the neurodegenerative diseases whose aggregation is affected by RNA binding.\n                <\/jats:p>","DOI":"10.64898\/2026.06.02.729610","type":"posted-content","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T22:40:20Z","timestamp":1780699220000},"source":"Crossref","is-referenced-by-count":0,"title":["A\u03b2 Aggregates Bind the U1 Spliceosomal Ribonucleoprotein in Alzheimer Disease Brain"],"prefix":"10.64898","author":[{"given":"Youqi","family":"Tao","sequence":"first","affiliation":[{"name":"Ann Romney Center for Neurology Diseases, Department of Neurology, Brigham and Women\u2019s Hospital, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna E.","family":"Francis","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurology Diseases, Department of Neurology, Brigham and Women\u2019s Hospital, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Liu","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurology Diseases, Department of Neurology, Brigham and Women\u2019s Hospital, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Watkins","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Stem Cell and Regenerative Biology Program, Division of Hematology\/Oncology, Boston Children\u2019s Hospital; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3689-554X","authenticated-orcid":false,"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis J.","family":"Selkoe","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurology Diseases, Department of Neurology, Brigham and Women\u2019s Hospital, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5013-0442","authenticated-orcid":false,"given":"Ryan A.","family":"Flynn","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Stem Cell and Regenerative Biology Program, Division of Hematology\/Oncology, Boston Children\u2019s Hospital; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA"},{"name":"Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA"},{"name":"Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8589-6891","authenticated-orcid":false,"given":"Andrew M.","family":"Stern","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurology Diseases, Department of Neurology, Brigham and Women\u2019s Hospital, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026060814200917000_2026.06.02.729610v1.1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201600057"},{"key":"2026060814200917000_2026.06.02.729610v1.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1310249110"},{"key":"2026060814200917000_2026.06.02.729610v1.3","doi-asserted-by":"crossref","unstructured":"Bishof, I. et al. 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