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001     276274
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024 7 _ |a 10.1016/j.parkreldis.2024.107256
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024 7 _ |a 1353-8020
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024 7 _ |a 1873-5126
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037 _ _ |a DZNE-2025-00253
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Espay, Alberto J
|b 0
245 _ _ |a The α-synuclein seed amplification assay: Interpreting a test of Parkinson's pathology.
260 _ _ |a Amsterdam [u.a.]
|c 2025
|b Elsevier Science
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520 _ _ |a 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.
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650 _ 7 |a Parkinson's disease
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650 _ 7 |a Seed amplification assay
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650 _ 7 |a Seeding
|2 Other
650 _ 7 |a α-synuclein
|2 Other
650 _ 7 |a alpha-Synuclein
|2 NLM Chemicals
650 _ 2 |a alpha-Synuclein: cerebrospinal fluid
|2 MeSH
650 _ 2 |a alpha-Synuclein: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Parkinson Disease: diagnosis
|2 MeSH
650 _ 2 |a Parkinson Disease: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Parkinson Disease: metabolism
|2 MeSH
700 1 _ |a Lees, Andrew J
|b 1
700 1 _ |a Cardoso, Francisco
|b 2
700 1 _ |a Frucht, Steven J
|b 3
700 1 _ |a Erskine, Daniel
|b 4
700 1 _ |a Sandoval, Ivette M
|b 5
700 1 _ |a Bernal-Conde, Luis Daniel
|b 6
700 1 _ |a Sturchio, Andrea
|b 7
700 1 _ |a Imarisio, Alberto
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700 1 _ |a Hoffmann, Christian
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700 1 _ |a Montemagno, Kora T
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700 1 _ |a Milovanovic, Dragomir
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700 1 _ |a Halliday, Glenda M
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700 1 _ |a Manfredsson, Fredric P
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773 _ _ |a 10.1016/j.parkreldis.2024.107256
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|t Parkinsonism & related disorders
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856 4 _ |u https://pub.dzne.de/record/276274/files/DZNE-2025-00253_Restricted.pdf
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