TY  - JOUR
AU  - Espay, Alberto J
AU  - Lees, Andrew J
AU  - Cardoso, Francisco
AU  - Frucht, Steven J
AU  - Erskine, Daniel
AU  - Sandoval, Ivette M
AU  - Bernal-Conde, Luis Daniel
AU  - Sturchio, Andrea
AU  - Imarisio, Alberto
AU  - Hoffmann, Christian
AU  - Montemagno, Kora T
AU  - Milovanovic, Dragomir
AU  - Halliday, Glenda M
AU  - Manfredsson, Fredric P
TI  - The α-synuclein seed amplification assay: Interpreting a test of Parkinson's pathology.
JO  - Parkinsonism & related disorders
VL  - 131
SN  - 1353-8020
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - DZNE-2025-00253
SP  - 107256
PY  - 2025
AB  - 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.
KW  - alpha-Synuclein: cerebrospinal fluid
KW  - alpha-Synuclein: metabolism
KW  - Humans
KW  - Parkinson Disease: diagnosis
KW  - Parkinson Disease: cerebrospinal fluid
KW  - Parkinson Disease: metabolism
KW  - Parkinson's disease (Other)
KW  - Seed amplification assay (Other)
KW  - Seeding (Other)
KW  - α-synuclein (Other)
KW  - alpha-Synuclein (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39794217
DO  - DOI:10.1016/j.parkreldis.2024.107256
UR  - https://pub.dzne.de/record/276274
ER  -