Abstract
Background:
Parkinson's disease (PD) is a common neurodegenerative disorder of unknown etiology. The characteristic α‐synuclein aggregation of PD is also a feature of Sanfilippo syndrome, a storage disorder caused by α‐N‐acetylglucosaminidase (NAGLU) gene mutations. We explored genetic links between these disorders and studied the pathology of Sanfilippo syndrome to investigate a common pathway toward α‐synuclein aggregation.
Methods:
We typed the 2 single‐nucleotide polymorphisms that tag the common haplotypes of NAGLU in 926 PD patients and 2308 controls and also stained cortical tissue from 2 cases of Sanfilippo A syndrome using the anti‐α‐synuclein antibody, Per7.
Results:
Allelic analysis showed an association between rs2071046 and risk for PD (P 1.3 × 10^−3^). Intracellular α‐synuclein accumulation was observed in the cortical tissue of both Sanfilippo A syndrome cases.
Conclusions:
This study suggests a possible role of NAGLU in susceptibility to PD while extending evidence for α‐synuclein aggregation in the brain in lysosomal storage disorders. Our findings support a mechanism involving lysosomal dysfunction more generally in the pathogenesis of PD. © 2011 Movement Disorder Society