Possible association of missense mutation (Gly-63Glu) of the neurotrophin-3 gene with Alzheimer's disease in Japanese

Several lines of evidence have suggested a possible involvement of neurotrophic factors in the pathogenesis of neurodegenerative disease. We examined whether a missense mutation (Gly(-63)Glu) of the neurotrophin-3 (NT-3) gene is associated with Alzheimer's disease (AD) in a Japanese sample of 123 patients and 215 controls. We found that homozygotes or heterozygotes for the mutated type (Glu(-63)) were significantly more common among the patients than the controls (P = 0.013, odds ratio 1.77, 95% Cl 1.12-2.79). The mutated type was more frequent among the patients than the controls (P = 0.011, odds ratio 1.63, 95%Cl 1.11-2.38). This association between NT-3 and AD was more prominent among those who did not carry the epsilon 4 allele of the apolipoprotein E gene than those who carried the epsilon 4 allele. Our results suggest that the Glu(-63) allele of the NT-3 gene by itself or another mutation nearby which would be in linkage disequilibrium to the mutation is a risk factor for AD. (C) 1998 Elsevier Science Ireland Ltd.