Alpha-synuclein quantitative seed amplification assay predicts conversion to dementia

Research output: Contribution to journal › Research article › Contributed › peer-review

Contributors

  • Stefan Bräuer - , Department of Neurology, University Hospital Carl Gustav Carus Dresden, German Center for Neurodegenerative Diseases (DZNE) - Partner Site Dresden (Author)
  • Verena Sondermann - , Department of Neurology, German Center for Neurodegenerative Diseases (DZNE) - Partner Site Dresden (Author)
  • Iñaki Schniewind - , Department of Neurology, University Hospital Carl Gustav Carus Dresden, German Center for Neurodegenerative Diseases (DZNE) - Partner Site Dresden (Author)
  • Tom Hähnel - , Department of Neurology, University Hospital Carl Gustav Carus Dresden, German Center for Neurodegenerative Diseases (DZNE) - Partner Site Dresden (Author)
  • Elisabeth Dinter - , Department of Neurology, German Center for Neurodegenerative Diseases (DZNE) - Partner Site Dresden (Author)
  • Luca Kleineidam - , University of Bonn Medical Center, German Center for Neurodegenerative Diseases (DZNE) - Partner Site Bonn (Author)
  • Melina Stark - , University of Bonn Medical Center, German Center for Neurodegenerative Diseases (DZNE) - Partner Site Bonn (Author)
  • Matthias Schmid - , German Center for Neurodegenerative Diseases (DZNE) - Partner Site Bonn, University of Bonn Medical Center (Author)
  • Sebastian Sodenkamp - , University of Tübingen, German Center for Neurodegenerative Diseases (DZNE) - Partner Site Tübingen (Author)
  • Christoph Laske - , Hertie‐Institute for Clinical Brain Research, University of Tübingen (Author)
  • Eike Spruth - , German Center for Neurodegenerative Diseases (DZNE) - - Partner Site Berlin (Author)
  • Josef Priller - , Technical University of Munich, German Center for Mental Health (DZPG) Partner Site Munich-Augsburg (Author)
  • Daniel Janowitz - , Hospital of the Ludwig-Maximilians-University (LMU) Munich (Author)
  • Katharina Bürger - , German Center for Neurodegenerative Diseases (DZNE) (Author)
  • Ingo Kilimann - , German Center for Neurodegenerative Diseases (DZNE) - Partner Site Rostock/Greifswald (Author)
  • Stefan Teipel - , German Center for Neurodegenerative Diseases (DZNE) - Partner Site Rostock/Greifswald (Author)
  • Alexander Storch - , Rostock University Medical Centre (Author)
  • Niels Hansen - , University Medical Center Göttingen (Author)
  • Jens Wiltfang - , University of Aveiro (Author)
  • Wenzel Glanz - , German Center for Neurodegenerative Diseases (DZNE) - Partner Site Magdeburg (Author)
  • Emrah Düzel - , Otto von Guericke University Magdeburg (Author)
  • Lukas Preis - , Charité – Universitätsmedizin Berlin (Author)
  • Oliver Peters - , Experimental and Clinical Research Center (ECRC) (Author)
  • Julian Hellmann-Regen - , Experimental and Clinical Research Center (ECRC) (Author)
  • Michael Wagner - , University of Bonn Medical Center, German Center for Neurodegenerative Diseases (DZNE) - Partner Site Bonn (Author)
  • Alexander Bernhardt - , Hospital of the Ludwig-Maximilians-University (LMU) Munich (Author)
  • Johannes Levin - , Munich Cluster for Systems Neurology (SyNergy) (Author)
  • Gabor Petzold - , University Hospital Aachen (Author)
  • Marie Kronmüller - , German Center for Neurodegenerative Diseases (DZNE) - Partner Site Bonn (Author)
  • Anna Gamez - , German Center for Neurodegenerative Diseases (DZNE) - Partner Site Bonn (Author)
  • Annika Spottke - , University of Bonn Medical Center (Author)
  • Frederic Brosseron - , German Center for Neurodegenerative Diseases (DZNE) - Partner Site Bonn (Author)
  • Ayda Rostamzadeh - , RWTH Aachen University (Author)
  • Frank Jessen - , University Hospital Cologne (Author)
  • Andreas Hermann - , Rostock University Medical Centre (Author)
  • Klaus Fliessbach - , University of Bonn Medical Center (Author)
  • Anja Schneider - , University of Bonn Medical Center (Author)
  • Björn H Falkenburger - , Department of Neurology, University Hospital Carl Gustav Carus Dresden, German Center for Neurodegenerative Diseases (DZNE) - Partner Site Dresden (Author)

Abstract

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.

Details

Original languageEnglish
Article numbere71167
Number of pages11
Journal Alzheimer's & dementia : the journal of the Alzheimer's Association
Volume22
Issue number1
Publication statusPublished - 22 Jan 2026
Peer-reviewedYes

External IDs

PubMedCentral PMC12828062
ORCID /0000-0002-2387-526X/work/203813179
Scopus 105028349562

Keywords

Research priority areas of TU Dresden

DFG Classification of Subject Areas according to Review Boards

Subject groups, research areas, subject areas according to Destatis

ASJC Scopus subject areas

Keywords

  • Aged, Aged, 80 and over, Biomarkers/cerebrospinal fluid, Cohort Studies, Dementia/cerebrospinal fluid, Disease Progression, Female, Humans, Lewy Body Disease/cerebrospinal fluid, Male, Prognosis, alpha-Synuclein/cerebrospinal fluid, real-time quaking-induced conversion, alpha-synuclein, seed amplification assay, Alzheimer´s disease, dementia, Lewy body