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Prion protein gene M129 allele is a risk factor for Alzheimer's disease

M Gacia1, K Safranow, M Styczyńska

  • 1Department of Neurodegenerative Disorders, Medical Research Center, Polish Academy of Sciences, Warszawa, Poland.

Journal of Neural Transmission (Vienna, Austria : 1996)
|August 10, 2006
PubMed

Insights

The prion protein gene M129V polymorphism, specifically the MM genotype, is linked to an elevated risk of late-onset Alzheimer's disease (AD) in the Polish population, independent of APOE4 status.

Area of Science:

  • Neurogenetics
  • Alzheimer's Disease Research
  • Human Genetics

Background:

  • The prion protein gene (PRNP) M129V polymorphism is a known risk factor for Creutzfeldt-Jakob disease.
  • Recent meta-analyses suggest a potential link between homozygosity at codon 129 and an increased risk of Alzheimer's disease (AD).

Purpose of the Study:

  • To investigate if the PRNP M129V polymorphism acts as a risk factor for Alzheimer's disease in a Polish cohort.
  • To analyze the association between M129V genotypes and AD, considering early-onset and late-onset forms, and APOE4 status.

Main Methods:

  • Genotyping analysis of the PRNP M129V polymorphism in early-onset AD (EOAD) and late-onset AD (LOAD) patients and control groups from Poland.
  • Stratification of patient data based on APOE4 allele status to assess gene-gene interactions.

Main Results:

  • A statistically significant increase in the MM genotype and a decrease in the MV genotype frequency were observed in LOAD patients compared to controls.
  • In LOAD patients without the APOE4 allele, MM genotype frequency was significantly higher, and MV genotype frequency was significantly lower.
  • In LOAD patients with the APOE4 allele, only the MV genotype frequency was significantly lower than in controls.
  • No significant interaction was detected between APOE4 status and M129V polymorphism.

Conclusions:

  • The MM genotype of the PRNP M129V polymorphism is associated with an increased risk of LOAD in the Polish population.
  • This increased risk appears to be independent of APOE4 status, suggesting a distinct genetic contribution to LOAD pathogenesis.

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