Brain-derived Neurotrophic Factor Gene Polymorphism Affects Cognitive Function and Neurofilament Light Chain Level in Patients with Subcortical Ischaemic Vascular Dementia

Overview

Journal Front Aging Neurosci

Specialty Geriatrics

Date 2023 Oct 25

PMID 37876876

Authors

Xiaojuan Yao

Guotao Yang

Tingting Fang

Zhuo Tian

Yunyao Lu

Feifan Chen

Ping Che

Jingshan Chen

Nan Zhang

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the effects of brain-derived neurotrophic factor (BDNF) gene polymorphism on cognitive function, neuroimaging and blood biological markers in patients with subcortical ischaemic vascular dementia (SIVD).

Methods: A total of 81 patients with SIVD were included. According to their BDNF gene polymorphism, the participants were divided into the Val/Val ( = 26), Val/Met ( = 35), and Met/Met ( = 20) groups. A comprehensive neuropsychological evaluation and multimodal brain MRI scan were performed. MRI markers for small vessel disease were visually rated or quantitatively analysed. Moreover, 52 patients were further evaluated with blood marker assays, including amyloid beta (Aβ), phosphorylated tau at threonine-181 (P-tau181), glial fibrillary acidic protein (GFAP), total tau (T-tau) and neurofilament light chain (NfL).

Results: There were no significant differences in demographics, disease duration or MRI markers of small vessel disease between the three groups. Compared with the Val/Val and Val/Met groups, the Met/Met group showed worse performance in the verbal fluency test and higher levels of plasma NfL.

Conclusion: The rs6265 polymorphism of the BDNF gene is associated with semantic language fluency in patients with SIVD. The Met genotype may be a risk factor for cognitive impairment and neuronal injury.

References

Liguori M, Fera F, Gioia M, Valentino P, Manna I, Condino F . Investigating the role of brain-derived neurotrophic factor in relapsing-remitting multiple sclerosis. Genes Brain Behav. 2006; 6(2):177-83. DOI: 10.1111/j.1601-183X.2006.00245.x. View

Ridha B, Barnes J, van de Pol L, Schott J, Boyes R, Siddique M . Application of automated medial temporal lobe atrophy scale to Alzheimer disease. Arch Neurol. 2007; 64(6):849-54. DOI: 10.1001/archneur.64.6.849. View

Sachdev P, Kalaria R, OBrien J, Skoog I, Alladi S, Black S . Diagnostic criteria for vascular cognitive disorders: a VASCOG statement. Alzheimer Dis Assoc Disord. 2014; 28(3):206-18. PMC: 4139434. DOI: 10.1097/WAD.0000000000000034. View

Roman G, Erkinjuntti T, Wallin A, Pantoni L, Chui H . Subcortical ischaemic vascular dementia. Lancet Neurol. 2003; 1(7):426-36. DOI: 10.1016/s1474-4422(02)00190-4. View

Harrisberger F, Smieskova R, Schmidt A, Lenz C, Walter A, Wittfeld K . BDNF Val66Met polymorphism and hippocampal volume in neuropsychiatric disorders: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2015; 55:107-18. DOI: 10.1016/j.neubiorev.2015.04.017. View

Ramirez-Gomez L, Zheng L, Reed B, Kramer J, Mungas D, Zarow C . Neuropsychological Profiles Differentiate Alzheimer Disease from Subcortical Ischemic Vascular Dementia in an Autopsy-Defined Cohort. Dement Geriatr Cogn Disord. 2017; 44(1-2):1-11. PMC: 5789445. DOI: 10.1159/000477344. View

Nasreddine Z, Phillips N, Bedirian V, Charbonneau S, Whitehead V, Collin I . The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005; 53(4):695-9. DOI: 10.1111/j.1532-5415.2005.53221.x. View

Liu X, Che P, Xing M, Tian X, Gao C, Li X . Cerebral Hemodynamics and Carotid Atherosclerosis in Patients With Subcortical Ischemic Vascular Dementia. Front Aging Neurosci. 2021; 13:741881. PMC: 8645960. DOI: 10.3389/fnagi.2021.741881. View

Chen J, Yang X, Zhang Y, Zheng P, Wei C, Mao Z . Reference values for plasma neurofilament light chain (NfL) in healthy Chinese. Clin Chem Lab Med. 2020; 59(4):e153-e156. DOI: 10.1515/cclm-2020-1030. View

10.

Rezaei S, Asgari Mobarake K, Saberi A, Keshavarz P, Kazemnejad Leili E . Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and post-stroke dementia: a hospital-based study from northern Iran. Neurol Sci. 2016; 37(6):935-42. DOI: 10.1007/s10072-016-2520-2. View

11.

Egan M, Kojima M, Callicott J, Goldberg T, Kolachana B, Bertolino A . The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003; 112(2):257-69. DOI: 10.1016/s0092-8674(03)00035-7. View

12.

Bialecka M, Kurzawski M, Roszmann A, Robowski P, Sitek E, Honczarenko K . BDNF G196A (Val66Met) polymorphism associated with cognitive impairment in Parkinson's disease. Neurosci Lett. 2014; 561:86-90. DOI: 10.1016/j.neulet.2013.12.051. View

13.

Arevalo-Rodriguez I, Smailagic N, Roque I Figuls M, Ciapponi A, Sanchez-Perez E, Giannakou A . Mini-Mental State Examination (MMSE) for the detection of Alzheimer's disease and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev. 2015; (3):CD010783. PMC: 6464748. DOI: 10.1002/14651858.CD010783.pub2. View

14.

Altmann V, Schumacher-Schuh A, Rieck M, Callegari-Jacques S, R M Rieder C, Hutz M . Val66Met BDNF polymorphism is associated with Parkinson's disease cognitive impairment. Neurosci Lett. 2016; 615:88-91. DOI: 10.1016/j.neulet.2016.01.030. View

15.

Forgrave L, Ma M, Best J, DeMarco M . The diagnostic performance of neurofilament light chain in CSF and blood for Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis: A systematic review and meta-analysis. Alzheimers Dement (Amst). 2020; 11:730-743. PMC: 6939029. DOI: 10.1016/j.dadm.2019.08.009. View

16.

Wardlaw J, Smith E, Biessels G, Cordonnier C, Fazekas F, Frayne R . Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013; 12(8):822-38. PMC: 3714437. DOI: 10.1016/S1474-4422(13)70124-8. View

17.

Toh Y, Ng T, Tan M, Tan A, Chan A . Impact of brain-derived neurotrophic factor genetic polymorphism on cognition: A systematic review. Brain Behav. 2018; 8(7):e01009. PMC: 6043712. DOI: 10.1002/brb3.1009. View

18.

OBrien J, Thomas A . Vascular dementia. Lancet. 2015; 386(10004):1698-706. DOI: 10.1016/S0140-6736(15)00463-8. View

19.

Taylor W, Zuchner S, McQuoid D, Payne M, MacFall J, Steffens D . The brain-derived neurotrophic factor VAL66MET polymorphism and cerebral white matter hyperintensities in late-life depression. Am J Geriatr Psychiatry. 2008; 16(4):263-71. DOI: 10.1097/JGP.0b013e3181591c30. View

20.

Ninan I, Bath K, Dagar K, Perez-Castro R, Plummer M, Lee F . The BDNF Val66Met polymorphism impairs NMDA receptor-dependent synaptic plasticity in the hippocampus. J Neurosci. 2010; 30(26):8866-70. PMC: 2911131. DOI: 10.1523/JNEUROSCI.1405-10.2010. View