The Influence of BDNF Val66Met Polymorphism on Cognition, Cerebrospinal Fluid, and Neuroimaging Markers in Non-Demented Elderly

Xia, Hui; Wang, Min; Li, Jieqiong; Tan, Cheng; Cao, Xi‐Peng; Tan, Lan; Yu, Jin‐Tai; Initiative, Alzheimer’s Disease Neuroimaging

doi:10.3233/jad-180971

Cited by 7 publications

(3 citation statements)

References 58 publications

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“…High amyloid-beta load in the brains of cognitively normal older BDNF Met carriers, relative to Val homozygotes, has been linked with worse episodic memory and executive function [65] and with a steeper trajectory of cognitive decline over time [66]. In a similar study of older people without dementia, carriage of the Met allele was associated with greater entorhinal cortex atrophy and lower Mini-Mental State Examination scores specifically in those individuals with amyloid positivity only [67].…”

Section: Exploring the Link Between The Bdnf Val66met Polymorphism Anmentioning

confidence: 98%

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

et al. 2020

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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.

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Section: Exploring the Link Between The Bdnf Val66met Polymorphism Anmentioning

confidence: 98%

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

et al. 2020

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“…BDNF бере активну участь в керуванні міжклітинними та внутрішньоклітинними сигнальними шляхами, ефективно попереджуючи загибель нервових клітин. Сучасні дослідження свідчать про зв'язок генетичних поліморфізмів гену, що кодує BDNF, та рівнем когнітивних змін в осіб різних популяцій, зокрема при хворобі Альцгеймера та шизофренії (Eyileten et al, 2021;Mori et al, 2021;Xia et al, 2019). Унікальний вплив цього нейротрофіну на клітини головного мозку, а саме, стимуляція репаративних процесів та нейропластичності в центральній нервовій системі, зумовлює актуальність визначення динаміки змін його рівня при гострих порушеннях мозкового кровообігу та пошук вирішення проблеми доставки його до тканин мозку у якості перспективного методу лікування.…”

Section: вступunclassified

Нейротрофічний Фактор Мозку Як Маркер Відновлення Моторних Та Когнітивних Функцій У Гострому Періоді Кардіоемболічного Та Атеротромботичного Ішемічного Інсульту

Havlovska¹,

Lytvynenko

Shlykova³

et al. 2022

USMYJ

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cerebral ischemic stroke is one of the most common diseases leading to psycho-emotional, cognitive and movement disorders. Modern research is aimed at searching for biological markers of brain damage in the diagnosis of strokes, in particular physical, imaging, electrophysiological, histological, genetic and neuronal markers, the determination of which can accelerate differential diagnosis. The purpose of the study was to assess the level of brain-derived neurotrophic factor in the blood, the state of motor and cognitive functions in the acute period of ischemic stroke on days 1 and 14, as well as the possibility of using the level of blood-brain neurotrophic factor as a marker of restoration of the motor and cognitive functions in atherothrombotic and cardioembolic subtypes of ischemic stroke. The study included 34 people diagnosed with acute ischemic stroke. Depending on the results of the clinical examination, the patients were divided into 2 groups: group 1 - patients in whom ischemic stroke occurred due to atherosclerotic lesions of the vessels of the carotid system with the development of occlusion by the mechanism of atherothrombosis (17 people), group 2 - patients in whom ischemic stroke occurred against the background of damage to the vessels of the carotid system with the development of occlusion by the cardioembolic mechanism (17 people). To compare clinical and laboratory parameters, a control group was additionally identified (patients of the neurological department who did not have damage to the central nervous system - 11 people). Examination of patients was performed on 1 and 14 day of the disease. Motor functions were assessed by the degree of daily activity of life, which was determined by the Barthel index, the state of cognitive functions - by the scale of Mini-Mental State Examination Mental State Examination. The Bartel index on the 1st day of the acute period of ischemic stroke was in the range of mild dependence for the cardioembolic subtype and moderate for atherothrombotic. Within 14 days, the studied patients of both groups had the increased index to the level of complete independence in group 1 and mild dependence in group 2. Among the examined patients with ischemic stroke, average values on the MMSE scale were determined at the level of moderate cognitive deficit per day in both subtypes of ischemic stroke. Restoration of cognitive function within 14 days after ischemic stroke occurred only in the second group before mild cognitive impairment. The concentration of neurotrophic factor of the brain on the 1st day of ischemic stroke decreased sharply compared with the control group. The obtained results allow to consider the brain neurotrophic factor as a prognostic objective biomarker of the prognosis of the restoration of motor and cognitive functions and the severity of cardioembolic and atherothrombotic ischemic stroke.

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“…The Met66 allele has been associated with reduced serum levels and activity of BDNF and carriers of the Met66 allele have been shown to have lower levels of cortisol after exposure to stress as compared to Val/Val homozygotes (Jiang et al ., 2017; Fiocco et al ., 2020). Although there is evidence that the Met66 allele is associated with reductions in cognition (Egan et al ., 2003; Xia et al ., 2019), brain volume (Pezawas et al ., 2004) and AD pathology (Bian et al ., 2005; Vepsalainen et al ., 2005; Fukumoto et al ., 2010), whether this is associated with the HPA axis response remains to be determined.…”

Section: The Hpa Axis: a Moderator Of Health And Diseasementioning

confidence: 99%

Chronic stress and Alzheimer's disease: the interplay between the hypothalamic–pituitary–adrenal axis, genetics and microglia

et al. 2021

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Chronic psychosocial stress is increasingly being recognised as a risk factor for sporadic Alzheimer's disease (AD). The hypothalamic-pituitary-adrenal axis (HPA axis) is the major stress response pathway in the body and tightly regulates the production of cortisol, a glucocorticoid hormone. Dysregulation of the HPA axis and increased levels of cortisol are commonly found in AD patients and make a major contribution to the disease process. The underlying mechanisms remain poorly understood. In addition, within the general population there are interindividual differences in sensitivities to glucocorticoid and stress responses, which are thought to be due to a combination of genetic and environmental factors. These differences could ultimately impact an individuals' risk of AD. The purpose of this review is first to summarise the literature describing environmental and genetic factors that can impact an individual's HPA axis reactivity and function and ultimately AD risk. Secondly, we propose a mechanism by which genetic factors that influence HPA axis reactivity may also impact inflammation, a key driver of neurodegeneration. We hypothesize that these factors can mediate glucocorticoid priming of the immune cells of the brain, microglia, to become pro-inflammatory and promote a neurotoxic environment resulting in neurodegeneration. Understanding the underlying molecular mechanisms and identifying these genetic factors has implications for evaluating stress-related risk/progression to neurodegeneration, informing the success of interventions based on stress management and potential risks associated with the common use of glucocorticoids.

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The Influence of BDNF Val66Met Polymorphism on Cognition, Cerebrospinal Fluid, and Neuroimaging Markers in Non-Demented Elderly

Cited by 7 publications

References 58 publications

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

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

Chronic stress and Alzheimer's disease: the interplay between the hypothalamic–pituitary–adrenal axis, genetics and microglia

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