{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T14:57:37Z","timestamp":1793026657903,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["AG000546"],"award-info":[{"award-number":["AG000546"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG024904"],"award-info":[{"award-number":["U01 AG024904"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) pathology is defined by \u03b2\u2010amyloid (A\u03b2) plaques and neurofibrillary tau, but Lewy bodies (LBs; \ud835\udefc\u2010synuclein aggregates) are a common co\u2010pathology for which effective biomarkers are needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A validated \u03b1\u2010synuclein Seed Amplification Assay (SAA) was used on recent cerebrospinal fluid (CSF) samples from 1638 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 78 with LB\u2010pathology confirmation at autopsy. We compared SAA outcomes with neuropathology, A\u03b2 and tau biomarkers, risk\u2010factors, genetics, and cognitive trajectories.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>SAA showed 79% sensitivity and 97% specificity for LB pathology, with superior performance in identifying neocortical (100%) compared to limbic (57%) and amygdala\u2010predominant (60%) LB\u2010pathology. SAA+ rate was 22%, increasing with disease stage and age. Higher A\u03b2 burden but lower CSF p\u2010tau181 associated with higher SAA+ rates, especially in dementia. SAA+ affected cognitive impairment in MCI and Early\u2010AD who were already AD biomarker positive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>SAA is a sensitive, specific marker for LB\u2010pathology. Its increase in prevalence with age and AD stages, and its association with AD biomarkers, highlights the clinical importance of \u03b1\u2010synuclein co\u2010pathology in understanding AD's nature and 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>SAA shows 79% sensitivity, 97% specificity for LB\u2010pathology detection in AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>SAA positivity prevalence increases with disease stage and age.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Higher A\u03b2 burden, lower CSF p\u2010tau181 linked with higher SAA+ rates in dementia.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>SAA+ impacts cognitive impairment in early disease stages.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Study underpins need for wider LB\u2010pathology screening in AD treatment.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.13858","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T07:00:27Z","timestamp":1716274827000},"page":"5114-5131","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["A cross\u2010sectional study of \u03b1\u2010synuclein seed amplification assay in Alzheimer's disease neuroimaging initiative: Prevalence and associations with Alzheimer's disease biomarkers and cognitive function"],"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"}]},{"given":"Hirotaka","family":"Iwaki","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"},{"name":"DataTecnica LLC  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":"Jennifer","family":"Lamoureux","sequence":"additional","affiliation":[{"name":"Amprion Inc.  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