Journal Article

DZNE-2024-00880

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Aggregation-resistant alpha-synuclein tetramers are reduced in the blood of Parkinson's patients.

de Boni, L. ; Wallis, A. ; Hays Watson, A. ; Ruiz-Riquelme, A.Extern* ; Leyland, L.-A. ; Bourinaris, T. ; Hannaway, N. ; Wüllner, U.DZNE* ; Peters, O.DZNE* ; Priller, J.DZNE* ; Falkenburger, B. H.DZNE* ; Wiltfang, J.DZNE* ; Bähr, M.DZNE* ; Zerr, I.DZNE* ; Bürger, K.DZNE* ; Perneczky, R.DZNE* ; Teipel, S.DZNE* ; Löhle, M.DZNE* ; Hermann, W.DZNE* ; Schott, B.-H.DZNE* ; Brockmann, K.DZNE* ; Spottke, A.DZNE* ; Haustein, K. ; Breuer, P.Extern* ; Houlden, H. ; Weil, R. S. ; Bartels, T.

2024
EMBO Press Heidelberg

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Please use a persistent id in citations: doi:10.1038/s44321-024-00083-5

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.

Keyword(s): Humans (MeSH) ; alpha-Synuclein: metabolism (MeSH) ; alpha-Synuclein: blood (MeSH) ; Parkinson Disease: blood (MeSH) ; Parkinson Disease: metabolism (MeSH) ; Parkinson Disease: genetics (MeSH) ; Aged (MeSH) ; Male (MeSH) ; Female (MeSH) ; Middle Aged (MeSH) ; Protein Multimerization (MeSH) ; Protein Aggregates (MeSH) ; Parkinson’s disease ; Alpha-synuclein ; Blood ; Human ; Parkinson’s disease ; Tetramer ; alpha-Synuclein ; Protein Aggregates ; SNCA protein, human

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Contributing Institute(s):

1. Biomarker Parkinson's Disease (AG Wüllner)
2. Biomarker-Assisted Early Detection of Dementias (AG Peters)
3. Translational Neuropsychiatry (AG Priller)
4. Translational Parkinson Research (AG Falkenburger)
5. Molecular biomarkers for predictive diagnostics of neurodegenerative diseases (AG Wiltfang)
6. Clinical Dementia Research (Göttingen) (Clinical Dementia Research (Göttingen))
7. Translational Studies and Biomarker (AG Zerr)
8. Clinical Research (Munich) (Clinical Research (Munich))
9. Clinical Dementia Research (Rostock /Greifswald) (AG Teipel)
10. Non-Motor Symptoms in Parkinson's disease (AG Storch)
11. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)
12. Parkinson Genetics (AG Gasser)
13. Clinical Research Platform (CRP) (AG Spottke)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2024

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