biostudies-literatureLau HHCNIA NIH HHSParkinson Society CanadaNational Institute on AgingCanadian Institutes of Health Research72https://www.ebi.ac.uk/biostudies/studies/S-EPMC10155462biostudies-literatureUnknown11(1)Unique strains of α-synuclein aggregates have been postulated to underlie the spectrum of clinical and pathological presentations seen across the synucleinopathies. Whereas multiple system atrophy (MSA) is associated with a predominance of oligodendroglial α-synuclein inclusions, α-synuclein aggregates in Parkinson's disease (PD) preferentially accumulate in neurons. The G51D mutation in the SNCA gene encoding α-synuclein causes an aggressive, early-onset form of PD that exhibits clinical and neuropathological traits reminiscent of both PD and MSA. To assess the strain characteristics of G51D PD α-synuclein aggregates, we performed propagation studies in M83 transgenic mice by intracerebrally inoculating patient brain extracts. The properties of the induced α-synuclein aggregates in the brActa neuropathologica communicationsThe G51D SNCA mutation generates a slowly progressive α-synuclein strain in early-onset Parkinson's disease.PMC101554622016-924P30AG062421PJT-169042Lau HHCStuart EMao AHyman BTMehra SMartinez-Valbuena ISchmitt-Ulms CWatts JCSo RWLKovacs GGIngelsson MSilver NRGfalseThe G51D SNCA mutation generates a slowly progressive α-synuclein strain in early-onset Parkinson's disease.Unique strains of α-synuclein aggregates have been postulated to underlie the spectrum of clinical and pathological presentations seen across the synucleinopathies. Whereas multiple system atrophy (MSA) is associated with a predominance of oligodendroglial α-synuclein inclusions, α-synuclein aggregates in Parkinson's disease (PD) preferentially accumulate in neurons. The G51D mutation in the SNCA gene encoding α-synuclein causes an aggressive, early-onset form of PD that exhibits clinical and neuropathological traits reminiscent of both PD and MSA. To assess the strain characteristics of G51D PD α-synuclein aggregates, we performed propagation studies in M83 transgenic mice by intracerebrally inoculating patient brain extracts. The properties of the induced α-synuclein aggregates in the br2023-01-01T00:00:00Z2023 May2025-04-22T04:09:27.229Z2025-04-05T20:52:58.146ZS-EPMC101554623713831810.1186/s40478-023-01570-5