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@ARTICLE{Espay:276274,
author = {Espay, Alberto J and Lees, Andrew J and Cardoso, Francisco
and Frucht, Steven J and Erskine, Daniel and Sandoval,
Ivette M and Bernal-Conde, Luis Daniel and Sturchio, Andrea
and Imarisio, Alberto and Hoffmann, Christian and
Montemagno, Kora T and Milovanovic, Dragomir and Halliday,
Glenda M and Manfredsson, Fredric P},
title = {{T}he α-synuclein seed amplification assay: {I}nterpreting
a test of {P}arkinson's pathology.},
journal = {Parkinsonism $\&$ related disorders},
volume = {131},
issn = {1353-8020},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {DZNE-2025-00253},
pages = {107256},
year = {2025},
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.},
subtyp = {Review Article},
keywords = {alpha-Synuclein: cerebrospinal fluid / alpha-Synuclein:
metabolism / Humans / Parkinson Disease: diagnosis /
Parkinson Disease: cerebrospinal fluid / Parkinson Disease:
metabolism / Parkinson's disease (Other) / Seed
amplification assay (Other) / Seeding (Other) / α-synuclein
(Other) / alpha-Synuclein (NLM Chemicals)},
cin = {AG Milovanovic (Berlin)},
ddc = {610},
cid = {I:(DE-2719)1813002},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39794217},
doi = {10.1016/j.parkreldis.2024.107256},
url = {https://pub.dzne.de/record/276274},
}