The brain-derived neurotrophic factor Val66Met polymorphism and rate of decline in Alzheimer's disease.
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.
Chuu
Jenny Y-J
JY
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305-5485, and the VA Sierra Pacific Mental Illness Research Education and Clinical Center, Palo Alto, CA, USA.
Taylor
Joy L
JL
Tinklenberg
Jared
J
Noda
Art
A
Yesavage
Jerome
J
Murphy
Greer M
GM
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D019943:Amino Acid Substitution / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014633:Valine / Q000235:genetics*
D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; D014633:Valine