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About the Authors:
Ira Driscoll
* E-mail: [email protected]
Affiliations Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland, United States of America, Psychology Department, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, United States of America
Bronwen Martin
Affiliation: Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, Maryland, United States of America
Yang An
Affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland, United States of America
Stuart Maudsley
Affiliation: Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland, United States of America
Luigi Ferrucci
Affiliation: Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, United States of America
Mark P. Mattson
Affiliation: Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland, United States of America
Susan M. Resnick
Affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland, United States of America
Introduction
Alzheimer's disease (AD) is a fatal neurodegenerative disorder characterized by the progressive loss of both grey and white matter, and cognitive impairment. Understanding pathogenic mechanisms and identifying biological risks is imperative to the discovery of biomarkers for differential diagnosis and treatment, as well as pharmacological targets. Much effort has focused on the role of neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF), in both the pathogenesis and the disease course of AD [1], [2].
BDNF is expressed throughout the brain, especially in the prefrontal cortex and the hippocampus [3]. Reduced BDNF levels in various brain regions have been implicated in the pathogenesis of neurodegenerative and psychiatric disorders [2]. Although human findings derive primarily from investigations of an allelic variant of BDNF (Val66Met), cumulative physiological, genetic and neuroimaging findings all favor the idea that BDNF influences cognitive function [4]. Moreover, Val66Met has been related to smaller hippocampal volumes [3], [5], [6] , which in turn are associated with worse memory [7] and more rapid conversion to dementia [8]. The mechanisms underlying these BDNF associations with brain function and structure, however, remain unclear. It is also unclear whether there is a relationship between BDNF genotypes and BDNF measured in plasma.
There are only a limited number of studies examining the relationships between polymorphisms in BDNF gene and plasma BDNF. In rhesus monkeys, a Val to Met transition in the pro-BDNF domain, similar to a well-described variant in the human gene,...