biostudies-literatureAlegre-Abarrategui JNIA NIH HHSMedical Research CouncilNetwork of Centres of excellence in NeurodegenerationNIHR Imperial Biomedical Research CentreParkinson’s UKJean Shanks FoundationNational Institute on AgingMichael J. Fox Foundation for Parkinson's ResearchParkinson's UK681-704https://www.ebi.ac.uk/biostudies/studies/S-EPMC6800835biostudies-literatureUnknown138(5)Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy are neurodegenerative disorders resulting in progressive motor/cognitive deficits among other symptoms. They are characterised by stereotypical brain cell loss accompanied by the formation of proteinaceous aggregations of the protein α-synuclein (α-syn), being, therefore, termed α-synucleinopathies. Although the presence of α-syn inclusions is a common hallmark of these disorders, the exact nature of the deposited protein is specific to each disease. Different neuroanatomical regions and cellular populations manifest a differential vulnerability to the appearance of protein deposits, cell dysfunction, and cell death, leading to phenotypic diversity. The present review describes the multiple factors that contribute Acta neuropathologicaSelective vulnerability in α-synucleinopathies.PMC6800835P01 AG012411J-0901MR/P007058/1J-1403NIA AG12411J-1402Brimblecombe KRRoberts RFTilley BSBengoa-Vergniory NAlegre-Abarrategui JProukakis CVelentza-Almpani EfalseSelective vulnerability in α-synucleinopathies.Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy are neurodegenerative disorders resulting in progressive motor/cognitive deficits among other symptoms. They are characterised by stereotypical brain cell loss accompanied by the formation of proteinaceous aggregations of the protein α-synuclein (α-syn), being, therefore, termed α-synucleinopathies. Although the presence of α-syn inclusions is a common hallmark of these disorders, the exact nature of the deposited protein is specific to each disease. Different neuroanatomical regions and cellular populations manifest a differential vulnerability to the appearance of protein deposits, cell dysfunction, and cell death, leading to phenotypic diversity. The present review describes the multiple factors that contribute 2019-01-01T00:00:00Z2019 Nov2025-04-05T13:18:41.121Z2019-11-09T08:00:50ZS-EPMC68008353100606710.1007/s00401-019-02010-2