{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:27:35Z","timestamp":1791912455796,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,10,20]],"date-time":"2024-10-20T00:00:00Z","timestamp":1729382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Cerebrospinal fluid (CSF) \u03b1\u2010synuclein (\u03b1\u2010syn) seed amplification assay (SAA) is a sensitive and specific tool for detecting Lewy body co\u2010pathology in Alzheimer's disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A total of 1637 cross\u2010sectional and 407 longitudinal CSF samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were tested with SAA. We examined longitudinal dynamics of amyloid beta (A\u03b2), \u03b1\u2010syn seeds, and phosphorylated tau181 (p\u2010tau181), along with global and domain\u2010specific cognition in stable SAA+, stable SAA\u2212, and those who converted to SAA+ from SAA\u2212.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>SAA+ individuals had faster cognitive decline than SAA\u2212, notably in mild cognitive impairment, and presented with earlier symptom onset. SAA+ conversion was associated with CSF A\u03b242 positivity but did not impact the progression of either CSF A\u03b242 or CSF p\u2010tau181 status. CSF A\u03b242, p\u2010tau181, and \u03b1\u2010syn SAA were all strong predictors of clinical progression, particularly CSF A\u03b242. In vitro, CSF \u03b1\u2010syn SAA kinetic parameters were associated with participant demographics, clinical profiles, and cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These results highlight the interplay between amyloid and \u03b1\u2010syn and their association with disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Seed amplification assay (SAA) positivity was associated with greater cognitive decline and earlier symptom onset.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Thirty\u2010four Alzheimer's Disease Neuroimaging Initiative (ADNI) individuals progressed from SAA\u2212 to SAA+, that is, \u2248 5% conversion.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>SAA conversion was associated with amyloid beta (A\u03b2) pathology and greater cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>SAA status did not impact the progression of either CSF A\u03b242 or phosphorylated tau181 biomarkers.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Change in clinical diagnosis was associated with both Alzheimer's disease biomarkers and SAA.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>SAA kinetic parameters were associated with clinical features and progression.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14276","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T02:52:29Z","timestamp":1729479149000},"page":"8444-8460","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Association of CSF \u03b1\u2010synuclein seed amplification assay positivity with disease progression and cognitive decline: A longitudinal Alzheimer's Disease Neuroimaging Initiative study"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8644-7724","authenticated-orcid":false,"given":"Duygu","family":"Tosun","sequence":"first","affiliation":[{"name":"Department of Radiology and Biomedical Imaging University of California San Francisco  San Francisco California USA"},{"name":"Department of Veterans Affairs Medical Center Northern California Institute for Research and Education (NCIRE)  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Hausle","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Medical Center Northern California Institute for Research and Education (NCIRE)  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5371-8667","authenticated-orcid":false,"given":"Pamela","family":"Thropp","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Medical Center Northern California Institute for Research and Education (NCIRE)  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Concha\u2010Marambio","sequence":"additional","affiliation":[{"name":"R&amp;D Unit Amprion Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Lamoureux","sequence":"additional","affiliation":[{"name":"R&amp;D Unit Amprion Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russ","family":"Lebovitz","sequence":"additional","affiliation":[{"name":"R&amp;D Unit Amprion Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie M.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Perelman School of Medicine, University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew B.","family":"Singleton","sequence":"additional","affiliation":[{"name":"Center for Alzheimer's and Related Dementias National Institute on Aging and National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Weiner","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging University of California San Francisco  San Francisco California USA"},{"name":"Department of Veterans Affairs Medical Center Northern California Institute for Research and 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