Abstract
In humans, brain-derived neurotrophic factor (BDNF) has been shown to play a pivotal role in neurocognition, and its gene contains a functional polymorphism (Val66Met) that may explain individual differences in brain volume and memory-related activity.In this study, we enrolled 186 Alzheimer's disease (AD) patients who underwent 3D T1 magnetic resonance imaging, and explored the gray matter (GM) structural covariance networks (SCN). The patients were divided into three groups according to their genotype: Met/Met (n = 45), Val/Met (n = 86) and Val/Val (n = 55). Seed-based analysis was performed focusing on four SCN networks. Neurobehavioral scores served as the major outcome factor.Only peak cluster volumes of default mode medial temporal lobe network showed significant genotype interactions, of which the interconnected peak clusters showed dose-dependent genotype effects. There were also significant correlations between the cognitive test scores and interconnected-cluster volumes, especially in the orbitofrontal cortex.These findings support the hypothesis that BDNF rs6265 polymorphisms modulate entorhinal cortex-interconnected clusters and the valine allele was associated with stronger structural covariance patterns that determined the cognitive outcomes.
Highlights
Neurotrophins are a group of molecules which play a key role in regulating neural survival, development and maintenance
There were no significant differences in apolipoprotein E4 allele distribution, Mini-Mental State Examination (MMSE) scores, total or individual cognitive ability-screening instrument (CASI) scores, neuropsychiatric inventory (NPI) total scores or levels of cerebrovascular risk biomarkers among the groups
While our results suggest that there was no direct effect of brain-derived neurotrophic factor (BDNF) genotype on hippocampal or entorhinal volume, we found that the BDNF genotype may modulate the default mode network (DMN) medial temporal lobe subsystem structural covariance patterns, of which the increased correlations between entorhinal seed and peak clusters demonstrated the genetic dosage effect of the Val allele
Summary
Neurotrophins are a group of molecules which play a key role in regulating neural survival, development and maintenance. The Met allele carriers have been shown to have poorer episodic memory, and this may be reflected in lower activities of BDNF with impaired neuronal processing and trafficking [9]. A recent metaanalysis study [10] showed no significant associations between the BDNF Val66Met polymorphism and the risk of developing AD in dominant (Met vs Val/Val), recessive (Met/Met vs Val) and additive (Met/Met vs Val/Val) carriers. Another meta-analysis reported that the Met allele conferred susceptibility to AD in women but not in men [11]
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