{"doi":"10.1002/alz.13858","title":"A cross‐sectional study of α‐synuclein seed amplification assay in Alzheimer's disease neuroimaging initiative: Prevalence and associations with Alzheimer's disease biomarkers and cognitive function","abstract":"INTRODUCTION: Alzheimer's disease (AD) pathology is defined by β-amyloid (Aβ) plaques and neurofibrillary tau, but Lewy bodies (LBs; 𝛼-synuclein aggregates) are a common co-pathology for which effective biomarkers are needed. METHODS: A validated α-synuclein Seed Amplification Assay (SAA) was used on recent cerebrospinal fluid (CSF) samples from 1638 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 78 with LB-pathology confirmation at autopsy. We compared SAA outcomes with neuropathology, Aβ and tau biomarkers, risk-factors, genetics, and cognitive trajectories. RESULTS: SAA showed 79% sensitivity and 97% specificity for LB pathology, with superior performance in identifying neocortical (100%) compared to limbic (57%) and amygdala-predominant (60%) LB-pathology. SAA+ rate was 22%, increasing with disease stage and age. Higher Aβ burden but lower CSF p-tau181 associated with higher SAA+ rates, especially in dementia. SAA+ affected cognitive impairment in MCI and Early-AD who were already AD biomarker positive. DISCUSSION: SAA is a sensitive, specific marker for LB-pathology. Its increase in prevalence with age and AD stages, and its association with AD biomarkers, highlights the clinical importance of α-synuclein co-pathology in understanding AD's nature and progression. HIGHLIGHTS: SAA shows 79% sensitivity, 97% specificity for LB-pathology detection in AD. SAA positivity prevalence increases with disease stage and age. Higher Aβ burden, lower CSF p-tau181 linked with higher SAA+ rates in dementia. SAA+ impacts cognitive impairment in early disease stages. Study underpins need for wider LB-pathology screening in AD treatment.","journal":"Alzheimer s & Dementia","year":2024,"id":417139,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":80,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7485,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1203357,"name":"Zachary Hausle","orcid":null,"position":1,"is_corresponding":false},{"id":252389,"name":"Hirotaka Iwaki","orcid":"0000-0002-8982-7885","position":2,"is_corresponding":false},{"id":1115440,"name":"Pamela Thropp","orcid":"0009-0006-5371-8667","position":3,"is_corresponding":false},{"id":483745,"name":"Jennifer Lamoureux","orcid":null,"position":4,"is_corresponding":false},{"id":107087,"name":"Edward B. Lee","orcid":"0000-0002-4589-1180","position":5,"is_corresponding":false},{"id":1010236,"name":"Karen MacLeod","orcid":null,"position":6,"is_corresponding":false},{"id":327450,"name":"Sean D. McEvoy","orcid":null,"position":7,"is_corresponding":false},{"id":21711,"name":"Michael A. Nalls","orcid":null,"position":8,"is_corresponding":false},{"id":308303,"name":"Richard J. Perrin","orcid":"0000-0002-3443-7716","position":9,"is_corresponding":false},{"id":27595,"name":"Andrew J. Saykin","orcid":"0000-0002-1376-8532","position":10,"is_corresponding":false},{"id":27605,"name":"Leslie M. Shaw","orcid":"0000-0002-7650-1210","position":11,"is_corresponding":false},{"id":6986,"name":"Andrew Singleton","orcid":"0000-0001-5606-700X","position":12,"is_corresponding":false},{"id":1010237,"name":"Russ Lebovitz","orcid":null,"position":13,"is_corresponding":false},{"id":51702,"name":"Michael W. Weiner","orcid":"0000-0002-0144-1954","position":14,"is_corresponding":false},{"id":252390,"name":"Cornelis Blauwendraat","orcid":"0000-0001-9358-8111","position":15,"is_corresponding":false},{"id":300139,"name":"for the Alzheimer's Disease Neuroimaging Initiative","orcid":null,"position":16,"is_corresponding":false},{"id":301454,"name":"Duygu Tosun","orcid":"0000-0001-8644-7724","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T01:56:50.743370Z","pmid":"38770829","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}