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However, Lewy body pathology (LBP) is found in \u2248 50% of AD and ADAD brains.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Using an \u03b1\u2010synuclein seed amplification assay (SAA) in cerebrospinal fluid (CSF) from asymptomatic (<jats:italic>n<\/jats:italic>\u00a0=\u00a026) and symptomatic (<jats:italic>n<\/jats:italic>\u00a0=\u00a027) ADAD mutation carriers, including 12 with known neuropathology, we investigated the timing of occurrence and prevalence of SAA positive reactivity in ADAD in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>No asymptomatic participant and only 11% (3\/27) of the symptomatic patients tested SAA positive. Neuropathology revealed LBP in 10\/12 cases, primarily affecting the amygdala or the olfactory areas. In the latter group, only the individual with diffuse LBP reaching the neocortex showed \u03b1\u2010synuclein seeding activity in CSF in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Results suggest that in ADAD LBP occurs later than AD pathology and often as amygdala\u2010 or olfactory\u2010predominant LBP, for which CSF \u03b1\u2010synuclein SAA has low sensitivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Cerebrospinal fluid (CSF) real\u2010time quaking\u2010induced conversion (RT\u2010QuIC) detects misfolded \u03b1\u2010synuclein in \u2248 10% of symptomatic autosomal dominant Alzheimer's disease (ADAD) patients.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>CSF RT\u2010QuIC does not detect \u03b1\u2010synuclein seeding activity in asymptomatic mutation carriers.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Lewy body pathology (LBP) in ADAD mainly occurs as olfactory only or amygdala\u2010predominant variants.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>LBP develops late in the disease course in ADAD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>CSF \u03b1\u2010synuclein RT\u2010QuIC has low sensitivity for focal, low\u2010burden LBP.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13818","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T04:39:50Z","timestamp":1714106390000},"page":"4351-4365","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["\u03b1\u2010Synuclein seed amplification assay detects Lewy body co\u2010pathology in autosomal dominant Alzheimer's disease late in the disease course and dependent on Lewy pathology burden"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5092-4306","authenticated-orcid":false,"given":"Johannes","family":"Levin","sequence":"first","affiliation":[{"name":"Department of Neurology LMU University Hospital, LMU Munich  Munich Germany"},{"name":"German Center for Neurodegenerative Diseases  Munich Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Baiardi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Quadalti","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna  Bologna 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