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

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.

Brain-Derived Neurotrophic Factor Polymorphism Influences Response to Single-Pulse Transcranial Magnetic Stimulation at Rest

“…Regulated activity-dependent secretion of BDNF is associated with synaptic plasticity and efficacy (3), strengthening excitatory (glutamatergic) synapses and weakening inhibitory (GABAergic) synapses (4). BDNF has been shown to play an influential role in several neurologic and psychiatric disorders such as mild traumatic brain injury, dementia, bipolar disorder and anxiety-related behaviors (2,(5)(6)(7)(8), and is also linked to impairment in cognitive abilities during normal aging (9).…”

Acute Brain-Derived Neurotrophic Factor DNA Methylation Trajectories in Cerebrospinal Fluid and Associations With Outcomes Following Severe Traumatic Brain Injury in Adults

“…17,18 It is interesting that the detrimental effect of higher BDNF action found in adults with TBI contrasts with most evidence in non-brain-injured populations in which lower BDNF action appears to confer risk for psychiatric and neurological conditions. [44][45][46][47][48][49][50][51][52][53][54][55][56] This suggests brain-injury-specific involvement of BDNF, possibly related to shifts in BDNF receptor balances in response to injury. 17,18,57 Regarding location and functionality of our suggestive CpG sites, all three are annotated to a BDNF promoter region (GRCh37/hg19, depending on the transcript of interest: cg26057780, chr11:27721277 north shore in gene body, 5' untranslated region [UTR], or transcription start site [TSS]; cg25328597, chr11:27722638 CpG island in gene body, 5'UTR, or TSS; cg25962210, chr11:27721222 north shore in gene body, 5'UTR, or TSS).…”

The Wither or Thrive Model of Resilience: an Integrative Framework of Dynamic Vulnerability and Resilience in the Face of Repeated Stressors During the COVID-19 Pandemic

“…A variety of biological factors has been proposed to influence the process of psychological resilience and vulnerability. Some of these factors include inflammation markers (Wang et al, 2018 ), various genetic markers such as FKBP5 gene (Feder et al, 2009 ; Russo et al, 2012 ), resting state connectivity (Workman et al, 2017 ), brain-derived neurotrophic factor (Brown et al, 2020 ; Rothman & Mattson, 2013 ), autonomic nervous system (Pereira, Campos & Sousa, 2017 ), hypothalamic pituitary adrenal (HPA) axis (Baumeister et al, 2014 ), glutamate (Reus et al, 2018 ), endocannabinoids (Maldonado et al, 2020 ), and structural brain abnormalities (Dedovic et al, 2009 ). Additionally, the physical health status of an individual, such as suffering from a chronic or acute disease, and lifestyle factors, such as diet and level of physical exercise, can serve as important biologically related predictors of the resilience-vulnerability (Alexandratos et al, 2012 ; Bremner et al, 2020 ; Carreira et al, 2018 ; Goubert & Trompetter, 2017 ; Pham et al, 2019 ).While neurobiological factors specific to an individual have been shown to affect the level of resilience-vulnerability of a person, similarly a range of psychological trait-like characteristics have also been posited to play a key role.…”