Aggregation-resistant alpha-synuclein tetramers are reduced in the blood of Parkinson’s patients

Boni, Laura de ; Wallis, Amber; Hays Watson, Aurelia; Ruiz-Riquelme, Alejandro ; Leyland, Louise-Ann; Bourinaris, Thomas; Hannaway, Naomi; Wüllner, Ullrich; Peters, Oliver; Priller, Josef ; Falkenburger, Björn H; Wiltfang, Jens ; Bähr, Mathias; Zerr, Inga; Bürger, Katharina; Perneczky, Robert ; Teipel, Stefan; Löhle, Matthias; Hermann, Wiebke; Schott, Björn-Hendrik ; Brockmann, Kathrin; Spottke, Annika; Haustein, Katrin; Breuer, Peter; Houlden, Henry; Weil, Rimona S und Bartels, Tim (2024): Aggregation-resistant alpha-synuclein tetramers are reduced in the blood of Parkinson’s patients. In: EMBO Molecular Medicine, Bd. 16, Nr. 7: S. 1657-1674

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Institut für Schlaganfall- und Demenzforschung (ISD) ; Medizin > Klinikum der LMU München > Klinik und Poliklink für Psychiatrie und Psychotherapie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1757-4684
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198