The BDNF Val66Met Polymorphism Modulates Resilience of Neurological Functioning to Brain Ageing and Dementia: A Narrative Review.

Donnamay T Brown,Katerina Cechova,David D Ward,Kimberley E Stuart,James C Vickers

doi:10.3390/brainsci10040195

Abstract

Brain-derived neurotropic factor (BDNF) is an abundant and multi-function neurotrophin in the brain. It is released following neuronal activity and is believed to be particularly important in strengthening neural networks. A common variation in the BDNF gene, a valine to methionine substitution at codon 66 (Val66Met), has been linked to differential expression of BDNF associated with experience-dependent plasticity. The Met allele has been associated with reduced production of BDNF following neuronal stimulation, which suggests a potential role of this variation with respect to how the nervous system may respond to challenges, such as brain ageing and related neurodegenerative conditions (e.g., dementia and Alzheimer’s disease). The current review examines the potential of the BDNF Val66Met variation to modulate an individual’s susceptibility and trajectory through cognitive changes associated with ageing and dementia. On balance, research to date indicates that the BDNF Met allele at this codon is potentially associated with a detrimental influence on the level of cognitive functioning in older adults and may also impart increased risk of progression to dementia. Furthermore, recent studies also show that this genetic variation may modulate an individual’s response to interventions targeted at building cognitive resilience to conditions that cause dementia.

Highlights

Neurotrophins are critical for cellular development, connectivity, plasticity and maintenance in the brain
(rs6265), widely known as the Brain-derived neurotropic factor (BDNF) Val66Met polymorphism, has received substantial attention, as hippocampal neurons transfected with the Met version of the single-nucleotide polymorphism (SNP) express 30% less secretion of BDNF protein upon stimulation than neurons transfected with the Val version, with no differences in constitutive release between these variants [10]
In addition to these key words, additional search terms of possible relevance were continuously identified from articles identified through database searches

Summary

Introduction

Neurotrophins are critical for cellular development, connectivity, plasticity and maintenance in the brain. Brain Sci. 2020, 10, 195 have a role in the refinement of active neural pathways through activity-dependent strengthening of co-active synapse terminals and elimination of inactive terminals [3]. BDNF works within seconds of release to influence synaptic function, over minutes to modify synaptic structure, and over hours to days to change genetic expression and protein synthesis [3]. In this regard, BDNF has a broad influence on both functional and structural forms of neural plasticity throughout the life course (for review, see [5])

Objectives

Methods

Findings

Conclusion