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From INSERM U360, Recherches Epidémiologiques en Neurologie et Psychopathologie (Drs. Berr, Dufouil, and Alperovitch), Hôpital de La Salpêtrière, Paris; and INSERM CJF95-05, Institut Pasteur de Lille (Drs. Richard, Amant, and Amouyel), Lille, France.
Address correspondence and reprint requests to Dr. C. Berr, INSERM U360, Recherches Epidémiologiques en Neurologie et Psychopathologie, Hôpital de la Salpêtrère, 75651-Paris Cedex 13, France.
Background: Little is known about the role of the prion protein (PrPsen/gene PRNP). PRNP knockout mice studies suggest that PrPsen may be involved in CNS degeneration. This observation prompted us to examine the influence of PRNP genetic variability on cognitive abilities in the elderly.
Methods: In a community-based sample of 1,163 subjects aged 59 to 71 years, we characterized the valine (Val) and methionine (Met) allele of the PRNP polymorphism at codon 129. The effect of this polymorphism was estimated on the Mini-Mental State Examination (MMSE) and on a global composite score built from a battery of nine different neuropsychological tests. The results were adjusted for age, gender, education, and apolipoprotein E (apoE) polymorphism.
Results: Cognitive impairment (MMSE score < 24) was present in 2.5% of the Met-Met individuals, 2.9% of the Met-Val individuals, and 7.0% of Val-Val subjects (p = 0.02). Subjects homozygous for the PRNP Val allele had a lower MMSE and global score than the two other genotypes (p< 0.003). This effect was of the same magnitude as that of the apoE
4 allele on cognitive performances. Both apoE 4 and PRNP Val allelic effects were additive.
Conclusion: This observation suggests that variability of the PRNP locus may be associated with cognitive performance in the elderly. This result, if confirmed, offers potential clues for the role of PRNP in the human brain.
The EVA study is organized under an agreement between INSERM and the Merck, Sharp and Dohme-Chibret Company, Paris, France.
Received March 11, 1998. Accepted in final form May 9, 1998.
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