%0 Journal Article
%A Espay, Alberto J
%A Lees, Andrew J
%A Cardoso, Francisco
%A Frucht, Steven J
%A Erskine, Daniel
%A Sandoval, Ivette M
%A Bernal-Conde, Luis Daniel
%A Sturchio, Andrea
%A Imarisio, Alberto
%A Hoffmann, Christian
%A Montemagno, Kora T
%A Milovanovic, Dragomir
%A Halliday, Glenda M
%A Manfredsson, Fredric P
%T The α-synuclein seed amplification assay: Interpreting a test of Parkinson's pathology.
%J Parkinsonism & related disorders
%V 131
%@ 1353-8020
%C Amsterdam [u.a.]
%I Elsevier Science
%M DZNE-2025-00253
%P 107256
%D 2025
%X 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.
%K alpha-Synuclein: cerebrospinal fluid
%K alpha-Synuclein: metabolism
%K Humans
%K Parkinson Disease: diagnosis
%K Parkinson Disease: cerebrospinal fluid
%K Parkinson Disease: metabolism
%K Parkinson's disease (Other)
%K Seed amplification assay (Other)
%K Seeding (Other)
%K α-synuclein (Other)
%K alpha-Synuclein (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39794217
%R 10.1016/j.parkreldis.2024.107256
%U https://pub.dzne.de/record/276274