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Dementia with lewy bodies: GBA1 mutations are associated with cerebrospinal fluid alpha‐synuclein profile
Author(s) -
Lerche Stefanie,
Machetanz Gerrit,
Wurster Isabel,
Roeben Benjamin,
Zimmermann Milan,
Pilotto Andrea,
Preische Oliver,
Stransky Elke,
Deuschle Christian,
Hauser AnnKathrin,
Schulte Claudia,
Lachmann Ingolf,
Waniek Katharina,
Gasser Thomas,
Berg Daniela,
Maetzler Walter,
Brockmann Kathrin
Publication year - 2019
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.27731
Subject(s) - dementia with lewy bodies , alpha synuclein , synucleinopathies , dementia , parkinson's disease , lewy body , medicine , neurology , pathology , psychiatry , disease
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‐beta 1‐42 , 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 DLB GBA_pathogenic compared to DLB GBA_mild and DLB GBA_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