Tosun, DuyguHausle, ZacharyIwaki, HirotakaThropp, PamelaLamoureux, JenniferLee, Edward B.MacLeod, KarenMcEvoy, SeanNalls, MichaelPerrin, Richard J.Saykin, Andrew J.Shaw, Leslie M.Singleton, Andrew B.Lebovitz, RussWeiner, Michael W.Blauwendraat, CornelisAlzheimer’s Disease Neuroimaging Initiative2024-10-152024-10-152024Tosun D, Hausle Z, Iwaki H, et al. 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. Alzheimers Dement. 2024;20(8):5114-5131. doi:10.1002/alz.13858https://hdl.handle.net/1805/43946Introduction: 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.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalAlzheimer's diseaseLewy bodySeed Amplification Assay (SAA)Co‐pathologyArticle