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• W2034497459 abstract "<h3>Context</h3> The brain-derived neurotrophic factor (<i>BDNF</i>) Val66Met (rs6265) polymorphism may predict the risk of Alzheimer disease (AD). However, genetic association studies of the<i>BDNF</i>gene with AD have produced equivocal results. Imaging-genetics strategies may clarify the manner in which<i>BDNF</i>gene variation predicts the risk of AD via characterization of its effects on at-risk structures or neural networks susceptible in this disorder. <h3>Objective</h3> To determine whether the<i>BDNF</i>Val66Met gene variant interacts with age to predict brain and cognitive measures in healthy volunteers across the adult lifespan in an intermediate phenotype pattern related to AD by examining (1) cortical thickness, (2) fractional anisotropy of white matter tracts (ie, white matter integrity), and (3) episodic memory performance. <h3>Design</h3> A cross-sectional study using genetics, high-resolution magnetic resonance imaging, diffusion tensor imaging, and cognitive testing in healthy individuals spanning the adult lifespan. <h3>Setting</h3> University hospital. <h3>Participants</h3> A total of 69 healthy volunteers ranging from 19 to 82 years of age. <h3>Main Outcome Measures</h3> The<i>BDNF</i>Val66Met genotype, apolipoprotein E genotype, cortical thickness, microstructural integrity of white matter tracts, and episodic memory performance were evaluated. <h3>Results</h3> The<i>BDNF</i>Val66Met polymorphism interacted with age to predict (1) cortical thickness (prominently at the entorhinal cortex and temporal gyri), (2) fractional anisotropy of white matter tracts (prominently at white matter tracts connecting to the medial temporal lobe), and (3) episodic memory performance. For each of these findings, the pattern was similar: valine/valine individuals in late life were susceptible, and in early adult life, methionine allele carriers demonstrated susceptibility. <h3>Conclusions</h3> The<i>BDNF</i>gene confers risk in an age-dependent manner on the brain structures and cognitive functions that are consistent with the neural circuitry vulnerable in the earliest stages of AD. Our novel findings provide convergent evidence in vivo for a<i>BDNF</i>genetic mechanism of susceptibility in an intermediate phenotype related to AD." @default.
• W2034497459 created "2016-06-24" @default.
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• W2034497459 date "2011-02-07" @default.
• W2034497459 modified "2023-10-18" @default.
• W2034497459 title "The Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Prediction of Neural Risk for Alzheimer Disease" @default.
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• W2034497459 doi "https://doi.org/10.1001/archgenpsychiatry.2010.194" @default.
• W2034497459 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21300947" @default.
• W2034497459 hasPublicationYear "2011" @default.
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