Affiliations: [a] Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA | [b] The VA Sierra Pacific Mental Illness Research Education and Clinical Center, Palo Alto, CA, USA
Correspondence:
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Corresponding author: Greer M. Murphy, Jr., M.D., Ph.D., Department of Psychiatry and Behavioral Sciences, MSLS P-104, Stanford University School of Medicine, Stanford, CA 94305-5485. Tel.: +1 650 725 0565; Fax: +1 650 498 7761; E-mail: gmurphy@stanford.edu.
Abstract: It is largely unknown why some patients with Alzheimer's disease (AD) decline cognitively more rapidly than others. Genetic differences among patients could influence rate of decline. Brain-derived neurotrophic factor (BDNF) is a neurotrophin important in the survival neurons and in memory function. BDNF levels are reduced in the brain in AD. The Val66Met polymorphism in the BDNF gene modifies neuronal BDNF secretion, and affects hippocampal function and memory performance. We tested the hypothesis that the BDNF Val66Met polymorphism influences rate of cognitive decline in AD. In a sample of 149 AD patients followed for an average of 3.9 years, we found no effect of BDNF Val66Met genotype on rate of change in the Mini Mental State Examination. Results were similar when we excluded patients taking an acetylcholinesterase inhibitor, those placed in a nursing home during the study, or those with a neuropathological diagnosis that included AD plus an entity other than AD. We also found no evidence that the effects of the BDNF Val66Met genotype depend on APOE genotype, which itself had no effect on rate of cognitive change. These findings suggest that the functional BDNF Val66Met variant is not a major determinant of rate of cognitive decline in AD.
Keywords: Alzheimer's disease, brain-derived neurotrophic factor, Mini Mental State Examination, cognitive decline, Apolipoprotein E, single nucleotide polymorphism, genotype
