%0 Journal Article
%A de Boni, Laura
%A Wallis, Amber
%A Hays Watson, Aurelia
%A Ruiz-Riquelme, Alejandro
%A Leyland, Louise-Ann
%A Bourinaris, Thomas
%A Hannaway, Naomi
%A Wüllner, Ullrich
%A Peters, Oliver
%A Priller, Josef
%A Falkenburger, Björn H
%A Wiltfang, Jens
%A Bähr, Mathias
%A Zerr, Inga
%A Bürger, Katharina
%A Perneczky, Robert
%A Teipel, Stefan
%A Löhle, Matthias
%A Hermann, Wiebke
%A Schott, Björn-Hendrik
%A Brockmann, Kathrin
%A Spottke, Annika
%A Haustein, Katrin
%A Breuer, Peter
%A Houlden, Henry
%A Weil, Rimona S
%A Bartels, Tim
%T Aggregation-resistant alpha-synuclein tetramers are reduced in the blood of Parkinson's patients.
%J EMBO molecular medicine
%V 16
%N 7
%@ 1757-4676
%C Heidelberg
%I EMBO Press
%M DZNE-2024-00880
%P 1657 - 1674
%D 2024
%X Synucleinopathies such as Parkinson's disease (PD) are defined by the accumulation and aggregation of the α-synuclein protein in neurons, glia and other tissues. We have previously shown that destabilization of α-synuclein tetramers is associated with familial PD due to SNCA mutations and demonstrated brain-region specific alterations of α-synuclein multimers in sporadic PD patients following the classical Braak spreading theory. In this study, we assessed relative levels of disordered and higher-ordered multimeric forms of cytosolic α-synuclein in blood from familial PD with G51D mutations and sporadic PD patients. We used an adapted in vitro-cross-linking protocol for human EDTA-whole blood. The relative levels of higher-ordered α-synuclein tetramers were diminished in blood from familial PD and sporadic PD patients compared to controls. Interestingly, the relative amount of α-synuclein tetramers was already decreased in asymptomatic G51D carriers, supporting the hypothesis that α-synuclein multimer destabilization precedes the development of clinical PD. Our data, therefore suggest that measuring α-synuclein tetramers in blood may have potential as a facile biomarker assay for early detection and quantitative tracking of PD progression.
%K Humans
%K alpha-Synuclein: metabolism
%K alpha-Synuclein: blood
%K Parkinson Disease: blood
%K Parkinson Disease: metabolism
%K Parkinson Disease: genetics
%K Aged
%K Male
%K Female
%K Middle Aged
%K Protein Multimerization
%K Protein Aggregates
%K Parkinson’s disease (Other)
%K Alpha-synuclein (Other)
%K Blood (Other)
%K Human (Other)
%K Parkinson’s disease (Other)
%K Tetramer (Other)
%K alpha-Synuclein (NLM Chemicals)
%K Protein Aggregates (NLM Chemicals)
%K SNCA protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%2 pmc:PMC11250827
%$ pmid:38839930
%R 10.1038/s44321-024-00083-5
%U https://pub.dzne.de/record/270708