Background: Patients with dementia with Lewy bodies reveal a variable pathology including alpha-synuclein, amyloid-beta, and Tau. Mutations in GBA1 are specifically associated with synucleinopathies. PD patients with GBA1 mutations show reduced CSF levels of total alpha-synuclein. Objective: Whether GBA1 mutations are associated with a CSF alpha-synuclein profile in dementia with Lewy bodies. Methods: Screening of the GBA1 gene and single-nucleotide polymorphisms in SNCA rs356220, APOE rs429358, and MAPT rs1052587 as well as CSF levels of total alpha-synuclein, amyloid-beta1-42, total-Tau, phospho-Tau, and neurofilament light chain were assessed in 100 dementia with Lewy bodies and 39 controls cross-sectionally. Results: Severity of GBA1 mutations was associated with a younger age at onset and higher prevalence of rapid eye movement sleep behavior disorder. CSF levels of total alpha-synuclein were lowest in DLBGBA_pathogenic compared to DLBGBA_mild and DLBGBA_wildtype. Conclusion: Similar to PD, pathogenic GBA1 mutations seem to be associated with CSF alpha-synuclein profiles in dementia with Lewy bodies. That might be useful for patient stratification for specific alpha-synuclein–lowering compounds. © 2019 International Parkinson and Movement Disorder Society.
Dementia with lewy bodies: GBA1 mutations are associated with cerebrospinal fluid alpha-synuclein profile
Pilotto A.;
2019-01-01
Abstract
Background: Patients with dementia with Lewy bodies reveal a variable pathology including alpha-synuclein, amyloid-beta, and Tau. Mutations in GBA1 are specifically associated with synucleinopathies. PD patients with GBA1 mutations show reduced CSF levels of total alpha-synuclein. Objective: Whether GBA1 mutations are associated with a CSF alpha-synuclein profile in dementia with Lewy bodies. Methods: Screening of the GBA1 gene and single-nucleotide polymorphisms in SNCA rs356220, APOE rs429358, and MAPT rs1052587 as well as CSF levels of total alpha-synuclein, amyloid-beta1-42, total-Tau, phospho-Tau, and neurofilament light chain were assessed in 100 dementia with Lewy bodies and 39 controls cross-sectionally. Results: Severity of GBA1 mutations was associated with a younger age at onset and higher prevalence of rapid eye movement sleep behavior disorder. CSF levels of total alpha-synuclein were lowest in DLBGBA_pathogenic compared to DLBGBA_mild and DLBGBA_wildtype. Conclusion: Similar to PD, pathogenic GBA1 mutations seem to be associated with CSF alpha-synuclein profiles in dementia with Lewy bodies. That might be useful for patient stratification for specific alpha-synuclein–lowering compounds. © 2019 International Parkinson and Movement Disorder Society.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
