Session Information
Date: Monday, September 23, 2019
Session Title: Genetics
Session Time: 1:45pm-3:15pm
Location: Les Muses Terrace, Level 3
Objective: Whether GBA1 mutations are associated with a CSF alpha-synuclein profile in DLB.
Background: Patients with dementia with Lewy bodies (DLB) 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.
Method: Screening of the GBA1 gene and single nucleotid 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 DLB patients and 39 controls cross-sectionally.
Results: Severity of GBA1 mutations was associated with a younger age at onset and higher prevalence of REM-sleep-behavior disorder. CSF levels of total alpha-synuclein were lowest in DLBGBA_severe compared to DLBGBA_mild and DLBwildtype.
Conclusion: Similar to PD, pathogenic GBA1 mutations seem to be associated with CSF alpha-synuclein profiles in DLB. That might be useful for patient stratification for specific alpha-synuclein-lowering compounds
To cite this abstract in AMA style:
S. Lerche, G. Machetanz, I. Wurster, B. Roeben, M. Zimmermann, A. Pilotto, A-K. Hauser, C. Schulte, I. Lachmann, T. Gasser, D. Berg, W. Maetzler, K. Brockmann. Dementia with Lewy bodies: GBA1 mutations are associated with cerebrospinal fluid alpha-synuclein profile [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/dementia-with-lewy-bodies-gba1-mutations-are-associated-with-cerebrospinal-fluid-alpha-synuclein-profile/. Accessed May 13, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/dementia-with-lewy-bodies-gba1-mutations-are-associated-with-cerebrospinal-fluid-alpha-synuclein-profile/