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

Neurobiol Aging. 2021 Dec:108:146-154. doi: 10.1016/j.neurobiolaging.2021.08.018. Epub 2021 Sep 4.


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.

Keywords: Alzheimer's disease; Amyloid-beta; BDNF; Subjective Cognitive Decline; Val66Met.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / genetics*
  • Aging / metabolism*
  • Aging / psychology
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Brain-Derived Neurotrophic Factor / blood
  • Brain-Derived Neurotrophic Factor / genetics*
  • Brain-Derived Neurotrophic Factor / physiology
  • Cognition*
  • Cognitive Dysfunction / genetics*
  • Cognitive Dysfunction / metabolism*
  • Dementia / genetics
  • Dementia / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Risk


  • Amyloid beta-Peptides
  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human

Supplementary concepts

  • Alzheimer Disease 10