NR ABHH
AU Berr,C.; Richard,F.; Dufouil,C.; Amant,C.; Alperovitch,A.; Amouyel,P.
TI Polymorphism of the prion protein is associated with cognitive impairment in the elderly: the EVA study.
QU Neurology 1998 Sep; 51(3): 734-7
PT journal article
AB BACKGROUND: Little is known about the role of the prion protein (PrP(sen)/gene PRNP). PRNP knockout mice studies suggest that PrP(sen) 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 epsilon4 allele on cognitive performances. Both apoE epsilon4 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.
IN Bei einem Kollektiv von 1.163 Personen im Alter von 59-71 Jahren wurden die kognitiven Fitneß und die Allelverteilung hinsichtlich des Codons 129 im Prionproteingen ermittelt. Unter Berücksichtigung von Alter, Bildung, Geschlecht Apolipoprotein-E-Polymorphismus glauben die Autoren, kognitive Defizite bei 2,5% der Met/Met-Homozygoten, 2,9% der Met/Val-Heterozygoten und signifikant davon abweichenden 7,0% der Val/Val-Homozygoten. Auch hinsichtlich 9 verschiedener neuropsychologischer Tests schnitten die Val/Val-Homozygoten durchschnittlich schlechter ab. Der "Effekt" war etwa so groß wie der der ApoE-epsilon4-Variante und verhielt sich zu diesem additiv.
MH Age Factors; Aged; Alleles; Apolipoproteins E/genetics; Cognition Disorders/*genetics; Education; Female; Genotype; Human; Male; Middle Age; Polymorphism (Genetics); Prions/*genetics; Psychological Tests
AD INSERM U360, Recherches Epidemiologiques en Neurologie et Psychopathologie, Hopital de La Salpetriere, Paris, France.
SP englisch
PO USA