Journal Article (Review Article)

DZNE-2025-00253

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The α-synuclein seed amplification assay: Interpreting a test of Parkinson's pathology.

Espay, A. J. ; Lees, A. J. ; Cardoso, F. ; Frucht, S. J. ; Erskine, D. ; Sandoval, I. M. ; Bernal-Conde, L. D. ; Sturchio, A. ; Imarisio, A. ; Hoffmann, C.DZNE* ; Montemagno, K. T. ; Milovanovic, D.DZNE* ; Halliday, G. M. ; Manfredsson, F. P.

2025
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.parkreldis.2024.107256

Abstract: The α-synuclein seed amplification assay (αSyn-SAA) sensitively detects Lewy pathology, the amyloid state of α-synuclein, in the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD). The αSyn-SAA harnesses the physics of seeding, whereby a superconcentrated solution of recombinant α-synuclein lowers the thermodynamic threshold (nucleation barrier) for aggregated α-synuclein to act as a nucleation catalyst ('seed') to trigger the precipitation (nucleation) of monomeric α-synuclein into pathology. This laboratory setup increases the signal for identifying a catalyst if one is present in the tissue examined. The result is binary: positive, meaning precipitation occurred, and a catalyst is present, or negative, meaning no precipitation, therefore no catalyst. Since protein precipitation via seeding can only occur at a concentration many-fold higher than the human brain, laboratory-elicited seeding does not mean human brain seeding. We suggest that a positive αSyn-SAA reveals the presence of pathological α-synuclein but not the underlying etiology for the precipitation of monomeric α-synuclein into its pathological form. Thus, a positive αSyn-SAA supports a clinical diagnosis of PD but cannot inform disease pathogenesis, ascertain severity, predict the rate of progression, define biology or biological subtypes, or monitor treatment response.

Keyword(s): alpha-Synuclein: cerebrospinal fluid (MeSH) ; alpha-Synuclein: metabolism (MeSH) ; Humans (MeSH) ; Parkinson Disease: diagnosis (MeSH) ; Parkinson Disease: cerebrospinal fluid (MeSH) ; Parkinson Disease: metabolism (MeSH) ; Parkinson's disease ; Seed amplification assay ; Seeding ; α-synuclein ; alpha-Synuclein

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Contributing Institute(s):

1. Molecular Neuroscience (AG Milovanovic (Berlin))

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2025

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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