Neither alpha-synuclein-preformed fibrils derived from patients with GBA1 mutations nor the host murine genotype significantly influence seeding efficacy in the mouse olfactory bulb.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive motor symptoms and alpha-synuclein (αsyn) aggregation in the nervous system. For unclear reasons, PD patients with certain GBA mutations (GBA-PD) have a more aggressive clinical progression. Two testable hypotheses that can potentially account for this phenomenon are that GBA1 mutations promote αsyn spread or drive the generation of highly pathogenic αsyn polymorphs (i.e., strains). We tested these hypotheses by treating homozygous GBA1 D409V knockin (KI) mice with human α-syn-preformed fibrils (PFFs) and treating wild-type mice (WT) with several αsyn-PFF polymorphs amplified from brain autopsy samples collected from patients with idiopathic PD and GBA-PD patients with either homozygous or he

SUBMITTER: Walton S 

PROVIDER: S-EPMC10473741 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature