BDNF-Met polymorphism and amyloid-beta in relation to cognitive decline in cognitively normal elderly: the SCIENCe project

NEUROBIOLOGY OF AGING

卷:108

Article

van den Bosch, Karlijn A.¹  Verberk, Inge M. W.^1,2  Ebenau, Jarith L.¹  van der Lee, Sven J.^1,4  Jansen, Iris E.^1,5  Prins, Niels D.^1,6  Scheltens, Philip¹  Teunissen, Charlotte E.^1,2  Van der Flier, Wiesje M.^1,3 

[1] Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Amsterdam UMC, De Boelelaan 1118, NL-1081 HZ Amsterdam, Netherlands

[2] Vrije Univ Amsterdam, Dept Clin Chem, Neurochem Lab, Amsterdam UMC, Amsterdam, Netherlands

[3] Vrije Univ Amsterdam, Dept Epidemiol & Data Sci, Amsterdam UMC, Amsterdam, Netherlands

[4] Amsterdam UMC, Dept Clin Genet, Amsterdam, Netherlands

[5] VU, Ctr Neurogen & Cognit Res, Dept Complex Trait Genet, Amsterdam, Netherlands

[6] Brain Res Ctr, Amsterdam, Netherlands

关键词: BDNF;    Val66Met;    Amyloid-beta;    Subjective Cognitive Decline;    Alzheimer's disease;   

DOI  :  10.1016/j.neurobiolaging.2021.08.018

来源: Elsevier

【 摘 要 】

Brain-derived neurotrophic factor (BNDF) plays a role in synapse integrity. We investigated in 398 cognitively normal adults (60 +/- 8years, 41% female, MMSE=28 +/- 1) the joint association of the Val66Met polymorphism of the BDNF gene (Met+/-) and plasma BDNF levels and abnormal cerebrospinal fluid (CSF) amyloid-beta status (A+/-) with cognitive decline and dementia risk. Age-, sex- and education-adjusted linear mixed models showed that compared to Met-A-, Met+ A+ showed steeper decline on tests of global cognition, memory, language, attention and executive functioning, while Met-A+ showed steeper decline on a smaller number of tests. There were no associations between Met+ A- and cognitive decline. Cox models showed that compared to Met-A-, Met+A+ participants were at increased risk of dementia (HR=8.8, 95%CI: 2.8-27.9), as were Met-A+ participants (HR=6.5, 95%CI: 2.2-19.5). Lower plasma BDNF was associated with an increased risk of progression to dementia in the A+ participants. Our results imply that Met-carriage on top of amyloid-beta pathology might increase rate of cognitive decline to dementia. (C) 2021 The Author(s). Published by Elsevier Inc.

【 授权许可】

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