title: 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.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Winder-Rhodes
authors.forename: Pablo
authors.initials: P
authors.lastname: Garcia-Reitböck
authors.forename: Maria
authors.initials: M
authors.lastname: Ban
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Evans
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Jacques
authors.forename: Anu
authors.initials: A
authors.lastname: Kemppinen
authors.forename: Thomas
authors.initials: T
authors.lastname: Foltynie
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Williams-Gray
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: Gavin
authors.initials: G
authors.lastname: Hudson
authors.forename: David J
authors.initials: DJ
authors.lastname: Burn
authors.forename: Liesl M
authors.initials: LM
authors.lastname: Allcock
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Sawcer
authors.forename: Roger A
authors.initials: RA
authors.lastname: Barker
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Spillantini
mesh_terms: D000118:Acetylglucosaminidase / Q000235:genetics*; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009084:Mucopolysaccharidosis III / Q000235:genetics* / Q000473:pathology*; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein; C033079:alpha-N-acetyl-D-glucosaminidase; D000118:Acetylglucosaminidase