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@ARTICLE{Bruer:276150,
author = {Bräuer, Stefan and Schniewind, Inaki and Dinter, Elisabeth
and Falkenburger, Björn H},
title = {{R}ecursive seed amplification detects distinct
α-synuclein strains in cerebrospinal fluid of patients with
{P}arkinson's disease.},
journal = {Acta Neuropathologica Communications},
volume = {13},
number = {1},
issn = {2051-5960},
address = {London},
publisher = {Biomed Central},
reportid = {DZNE-2025-00222},
pages = {13},
year = {2025},
abstract = {Parkinson's disease (PD) is a heterogeneous
neurodegenerative disorder with a wide range of clinical
phenotypes. Pathologically, it is characterized by neuronal
inclusions containing misfolded, fibrillar alpha-synuclein
(aSyn). Prion-like properties of aSyn contribute to the
spread of aSyn pathology throughout the nervous system as
the disease progresses. Utilizing these properties, seed
amplification assays (SAA) enable the detection of aSyn
pathology in living patients. We hypothesized that
structurally distinct aSyn aggregates, or strains, may
underlie the clinical heterogeneity of PD. To test this
hypothesis, we recursively amplified aSyn fibrils from the
cerebrospinal fluid (CSF) of 54 patients (34 people with PD
and 20 controls). These fibrils were then characterized
regarding SAA kinetic properties and detergent resistance.
In addition, cultured cells were transfected with SAA
products, and the extent of seeded aSyn pathology was
quantified by staining for phosphorylated aSyn followed by
automated high-throughput microscopy and image analysis. We
found that fibrils, amplified from CSF by recursive SAA,
exhibit two types of distinct biophysical properties and
have different seeding capacities in cells. These properties
are associated with clinical parameters and may therefore
help explain the clinical heterogeneity in PD. Measuring
aSyn strains may be relevant for prognosis and for therapies
targeting aSyn pathology.},
keywords = {Humans / alpha-Synuclein: cerebrospinal fluid / Parkinson
Disease: cerebrospinal fluid / Female / Male / Aged / Middle
Aged / Aged, 80 and over / Alpha-synuclein (Other) /
Parkinson’s disease (Other) / RT-QuIC (Other) / Seed
amplification assay (Other) / Strains (Other) /
alpha-Synuclein (NLM Chemicals) / SNCA protein, human (NLM
Chemicals)},
cin = {AG Falkenburger},
ddc = {610},
cid = {I:(DE-2719)1710012},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39833972},
pmc = {pmc:PMC11749544},
doi = {10.1186/s40478-024-01923-8},
url = {https://pub.dzne.de/record/276150},
}