TY  - JOUR
AU  - de Boni, Laura
AU  - Wallis, Amber
AU  - Hays Watson, Aurelia
AU  - Ruiz-Riquelme, Alejandro
AU  - Leyland, Louise-Ann
AU  - Bourinaris, Thomas
AU  - Hannaway, Naomi
AU  - Wüllner, Ullrich
AU  - Peters, Oliver
AU  - Priller, Josef
AU  - Falkenburger, Björn H
AU  - Wiltfang, Jens
AU  - Bähr, Mathias
AU  - Zerr, Inga
AU  - Bürger, Katharina
AU  - Perneczky, Robert
AU  - Teipel, Stefan
AU  - Löhle, Matthias
AU  - Hermann, Wiebke
AU  - Schott, Björn-Hendrik
AU  - Brockmann, Kathrin
AU  - Spottke, Annika
AU  - Haustein, Katrin
AU  - Breuer, Peter
AU  - Houlden, Henry
AU  - Weil, Rimona S
AU  - Bartels, Tim
TI  - Aggregation-resistant alpha-synuclein tetramers are reduced in the blood of Parkinson's patients.
JO  - EMBO molecular medicine
VL  - 16
IS  - 7
SN  - 1757-4676
CY  - Heidelberg
PB  - EMBO Press
M1  - DZNE-2024-00880
SP  - 1657 - 1674
PY  - 2024
AB  - 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.
KW  - Humans
KW  - alpha-Synuclein: metabolism
KW  - alpha-Synuclein: blood
KW  - Parkinson Disease: blood
KW  - Parkinson Disease: metabolism
KW  - Parkinson Disease: genetics
KW  - Aged
KW  - Male
KW  - Female
KW  - Middle Aged
KW  - Protein Multimerization
KW  - Protein Aggregates
KW  - Parkinson’s disease (Other)
KW  - Alpha-synuclein (Other)
KW  - Blood (Other)
KW  - Human (Other)
KW  - Parkinson’s disease (Other)
KW  - Tetramer (Other)
KW  - alpha-Synuclein (NLM Chemicals)
KW  - Protein Aggregates (NLM Chemicals)
KW  - SNCA protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11250827
C6  - pmid:38839930
DO  - DOI:10.1038/s44321-024-00083-5
UR  - https://pub.dzne.de/record/270708
ER  -