Journal
NEUROBIOLOGY OF AGING
Volume 35, Issue 4, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2013.09.019
Keywords
Parkinson's disease/Parkinsonism; GBA; Dementia; Gaucher disease
Categories
Funding
- Research Committee of CNS Degenerative Diseases [22790829, 23791003, 80218510, 21591098]
- Ministry of Health, Labour and Welfare of Japan [22140901]
- Japanese Ministry of Education, Culture, Sports, Science, and Technology [23111003, 23129506]
- Japanese Ministry of Health, Labor and Welfare [22140901, 23111003, 20261501, 22140501]
- JST, CREST
- Grants-in-Aid for Scientific Research [25860725, 25461291, 23129506, 23791003, 21591098, 22790829] Funding Source: KAKEN
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The glucocerebrosidase gene (GBA) is a known risk factor of Parkinson's disease (PD). We sequenced entire coding exons and exon/intron boundaries of GBA in 147 Japanese familial PD (FPD) patients from 144 families and 100 unrelated control subjects. Twenty-seven of 144 (18.8%) of index patients were heterozygous for known Gaucher disease mutations, suggesting that GBA heterozygous mutations are strongly associated with FPD (odds ratio = 22.9, 95% confidence interval = 3.1-171.2). The frequency was significantly higher in autosomal dominant PD (ADPD) compared with autosomal recessive PD. According to clinical assessments, PD patients with GBA mutations exhibited typical manifestations of PD or dementia with Lewy bodies (DLB), such as L-dopa responsive parkinsonism with psychiatric problems and/or cognitive decline. Interestingly, they also presented with reduced myocardial I-123-meta-iodobenzylguanidine uptake. Our findings suggest that heterozygous GBA mutations are strong risk factors in FPD, especially for autosomal dominant PD. Some patients with GBA heterozygous mutations develop clinical features of DLB. We speculate that GBA dysfunction may promote Lewy body formation, resulting in more severe PD or DLB phenotypes that are inherited in families. (C) 2014 Published by Elsevier Inc.
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