Genetic and pathological links between Parkinson's disease and the lysosomal disorder Sanfilippo syndrome

Mov Disord. 2012 Feb;27(2):312-5. doi: 10.1002/mds.24029. Epub 2011 Nov 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosaminidase / genetics*
  • Aged
  • Cohort Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mucopolysaccharidosis III / genetics*
  • Mucopolysaccharidosis III / pathology*
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology*
  • Polymorphism, Single Nucleotide / genetics*
  • alpha-Synuclein / metabolism


  • alpha-Synuclein
  • alpha-N-acetyl-D-glucosaminidase
  • Acetylglucosaminidase