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Prion protein codon 129 genotype prevalence is altered in primary progressive aphasia

Xiaohong Li1, Lewis P Rowland, Hiroshi Mitsumoto

  • 1Department of Neurology, Pritzker School of Medicine and Center for Comprehensive Care and Research on Memory Disorders, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA.

Annals of Neurology
|November 30, 2005
PubMed

Insights

The prion protein gene (PRNP) codon 129 genotype is not a risk factor for Alzheimer's disease or ALS. However, heterozygosity at PRNP codon 129 is strongly associated with primary progressive aphasia (PPA).

Area of Science:

  • Neurogenetics
  • Neurodegenerative Diseases
  • Prion Biology

Background:

  • The prion protein (PrP) is implicated in prion diseases, with potential roles in other neurodegenerative conditions.
  • A common polymorphism in the prion protein gene (PRNP) at codon 129 (Met/Val) influences prion disease risk and presentation.
  • Altered genotype frequencies may indicate PrP involvement in non-prion neurodegenerative diseases.

Purpose of the Study:

  • To investigate the association between PRNP codon 129 polymorphism and neurodegenerative diseases.
  • To compare genotype distributions in Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and primary progressive aphasia (PPA) against healthy controls.

Main Methods:

  • A case-control study design was employed.
  • Genotype distributions of PRNP codon 129 were analyzed in 281 AD, 256 ALS, 39 PPA patients, and 415 healthy controls.
  • Statistical analyses determined disease-specific genotype associations.

Main Results:

  • PRNP codon 129 genotype distribution was similar in healthy controls, AD, and ALS groups.
  • A significant overrepresentation of the heterozygous state (Met/Val) was observed in PPA patients (OR, 8.47).

Conclusions:

  • The PRNP codon 129 genotype is not supported as a risk factor for AD or ALS.
  • The strong association between PRNP codon 129 heterozygosity and PPA suggests a potential role for PrP in this rare neurodegenerative condition.
  • Further research is warranted to elucidate the role of PrP and its genetic variations in the etiology of PPA.

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