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000276150 1001_ $$0P:(DE-2719)9001805$$aBräuer, Stefan$$b0$$eFirst author$$udzne
000276150 245__ $$aRecursive seed amplification detects distinct α-synuclein strains in cerebrospinal fluid of patients with Parkinson's disease.
000276150 260__ $$aLondon$$bBiomed Central$$c2025
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000276150 520__ $$aParkinson'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.
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000276150 650_7 $$2Other$$aAlpha-synuclein
000276150 650_7 $$2Other$$aParkinson’s disease
000276150 650_7 $$2Other$$aRT-QuIC
000276150 650_7 $$2Other$$aSeed amplification assay
000276150 650_7 $$2Other$$aStrains
000276150 650_7 $$2NLM Chemicals$$aalpha-Synuclein
000276150 650_7 $$2NLM Chemicals$$aSNCA protein, human
000276150 650_2 $$2MeSH$$aHumans
000276150 650_2 $$2MeSH$$aalpha-Synuclein: cerebrospinal fluid
000276150 650_2 $$2MeSH$$aParkinson Disease: cerebrospinal fluid
000276150 650_2 $$2MeSH$$aFemale
000276150 650_2 $$2MeSH$$aMale
000276150 650_2 $$2MeSH$$aAged
000276150 650_2 $$2MeSH$$aMiddle Aged
000276150 650_2 $$2MeSH$$aAged, 80 and over
000276150 7001_ $$0P:(DE-2719)9000748$$aSchniewind, Inaki$$b1
000276150 7001_ $$0P:(DE-2719)9001016$$aDinter, Elisabeth$$b2$$udzne
000276150 7001_ $$0P:(DE-2719)2814178$$aFalkenburger, Björn H$$b3$$eLast author$$udzne
000276150 773__ $$0PERI:(DE-600)2715589-4$$a10.1186/s40478-024-01923-8$$gVol. 13, no. 1, p. 13$$n1$$p13$$tActa Neuropathologica Communications$$v13$$x2051-5960$$y2025
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