GBA Mutations Are Associated With Earlier Onset and Male Sex in Dementia With Lewy Bodies

Background: Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are Lewy body diseases characterized by similar pathological features. Several studies have shown a relation between alterations in the glucocerebrosidase gene (GBA) and the development of LB diseases. Here, we explored the role of GBA mutations in Spanish DLB patients.

Methods: GBA mRNA sequences were analyzed in a neuropathological (50 DLB, 43 PD, and 34 control brains) and in a clinical cohort (47 DLB patients and 131 unaffected individuals).

Results: Sixteen GBA mutation carriers were identified, 5 of which were brains with pure DLB. The most common mutation, E326K, was strongly associated with pure DLB and PD with dementia. GBA mutations were overrepresented in men and associated with earlier DLB onset.

Conclusions: GBA mutations are also an important risk factor for DLB development in the Spanish population, are associated with earlier disease onset, and are more prevalent in men. © 2015 International Parkinson and Movement Disorder Society.