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

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.

• Authors: Sophie E Winder-Rhodes, Pablo Garcia-Reitböck, Maria Ban, Jonathan R Evans, Thomas S Jacques, Anu Kemppinen, Thomas Foltynie, Caroline H Williams-Gray, Patrick F Chinnery, Gavin Hudson, David J Burn, Liesl M Allcock, Stephen J Sawcer, Roger A Barker, Maria Grazia Spillantini
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 27 Issue 2 Pg. 312-5 (Feb 2012) ISSN: 1531-8257 [Electronic] United States
• PMID: 22102531 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Movement Disorder Society.

Chemical References

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

Topics

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