Affiliations: [a] Alzheimer's Disease Research Unit, Department of Psychiatry, New Haven, CT, USA | [b] Division of Human Genetics, Department of Psychiatry, New Haven, CT, USA | [c] Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA
Correspondence:
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Corresponding author: Christopher H. van Dyck, MD, Alzheimer's Disease Research Unit, Yale University School of Medicine, One Church Street, Suite 600, New Haven, CT 06510, USA. Tel.: +1 203 764 8100; Fax: +1 203 764 8111; E-mail: [email protected].
Note: [] Communicated by Maire Percy
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.
Keywords: Activities of daily living, Alzheimer's disease, brain-derived neurotrophic factor, cognition, education, single nucleotide polymorphism
