BDNF variants, premorbid educational attainment, and disease characteristics in Alzheimer's disease: an exploratory study

Abstract

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that promotes neuronal survival, growth, and differentiation. The role of BDNF in learning and memory suggests that it may also modulate the clinical course of Alzheimer's disease (AD). This study aimed to determine whether BDNF genetic variants are related to premorbid educational attainment, progression of cognitive and functional decline, and associated neuropsychiatric symptoms in AD patients. A sample of AD subjects (N = 341) was genotyped for the BDNF polymorphisms: Val66Met, C270T, and G-712A. Subjects received tests of cognition and daily function at baseline and at multiple subsequent time points. They were also characterized for the frequency and severity of neuropsychiatric symptoms. There was a significant effect of Val66Met genotype on educational attainment (F = 7.49, df = 2,329, P = 0.00066), with Met/Met homozygotes having significantly lower education than both the Val/Met and Val/Val groups. No association was observed between any BDNF polymorphism and measures of cognitive or functional decline. The T-allele of the C270T polymorphism was associated with a higher prevalence of neuropsychiatric symptoms and specifically with the presence of hallucinations. The effect of the Val66Met polymorphism on premorbid educational attainment is intriguing and should be verified in a larger sample.

Fig. 1

Scatter plot of premorbid educational attainment (yrs) by Val66Met genotype in AD patients (N = 332). Each symbol denotes an individual subject. Val/Val and Val/Met subjects with 12 yrs education are separated into three rows for legibility. Horizontal bars indicate group means. There was a significant effect of Val66Met genotype on educational attainment (F = 7.49; df = 2,329; P = 0.00066, ANOVA). Post-hoc Tukey test showed that the Met/Met homozygote group had significantly lower education than both the Val/Met heterozygotes (P = 0.00056) and the Val/Val homozygotes (P = 0.0060). However, the Val/Met heterozygote and Val/Val homozygote groups did not differ from each other (P = 0.14).