Skip to main content

Alpha-synuclein quantitative seed amplification assay predicts conversion to dementia.

Alzheimer's & dementia : the journal of the Alzheimer's Association

Authors: Stefan Bräuer, Verena Sondermann, Iñaki Schniewind, Tom Hähnel, Elisabeth Dinter, Luca Kleineidam, Melina Stark, Matthias Schmid, Sebastian Sodenkamp, Christoph Laske, Eike Spruth, Josef Priller, Daniel Janowitz, Katharina Bürger, Ingo Kilimann, Stefan Teipel, Alexander Storch, Niels Hansen, Jens Wiltfang, Wenzel Glanz, Emrah Düzel, Lukas Preis, Oliver Peters, Julian Hellmann-Regen, Michael Wagner, Alexander Bernhardt, Johannes Levin, Gabor Petzold, Marie Kronmüller, Anna Gamez, Annika Spottke, Frederic Brosseron, Ayda Rostamzadeh, Frank Jessen, Andreas Hermann, Klaus Fliessbach, Anja Schneider, Björn H Falkenburger

INTRODUCTION: The alpha-synuclein seed amplification assay (SAA) has shown excellent performance in the detection of Lewy body pathology in cerebrospinal fluid (CSF). Lewy body pathology is prognostically relevant in patients at risk for dementia. Current assays only provide binary results, so there is a need to quantify the extent of pathology in living patients.

METHODS: In addition to the "standard" SAA, we developed a quantitative SAA (qnSAA) and measured 432 CSF samples (216 baseline-follow-up pairs).

RESULTS: qnSAA results correlated with cognitive performance. Seventy-five percent of participants with fast qnSAA kinetics converted to dementia in the observed interval. Overall, participants with fast qnSAA kinetics accounted for 27.3% of dementia converters in the entire cohort.

DISCUSSION: Findings demonstrate promising properties of qnSAA measurements in a cohort of patients at risk for dementia. qnSAA results showed improved prognostic relevance and have potential to measure target engagement of therapies against Lewy body pathology.

© 2026 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

PMID: 41572624

Participating cluster members