Brain-derived neurotrophic factor and TrkB expression in the "oldest-old," the 90+ Study: correlation with cognitive status and levels of soluble amyloid-beta

Neurobiol Aging. 2015 Dec;36(12):3130-3139. doi: 10.1016/j.neurobiolaging.2015.08.022. Epub 2015 Aug 29.


Factors associated with maintaining good cognition into old age are unclear. Decreased brain-derived neurotrophic factor (BDNF) contributes to memory loss in Alzheimer's disease (AD), and soluble assemblies of amyloid-beta (Aβ) and tau contribute to neurodegeneration. However, it is unknown whether AD-type neuropathology, soluble Aβ and tau, or levels of BDNF and its receptor tropomyosin-related kinase B (TrkB) correlate with dementia in the oldest-old. We examined these targets in postmortem Brodmann's areas 7 and 9 (BA7 and BA9) in 4 groups of subjects >90 years old: (1) no dementia/no AD pathology, (2) no dementia/AD pathology, (3) dementia/no AD pathology, (4) dementia/AD pathology. In BA7, BDNF messenger RNA correlated with Mini-Mental State Examination scores and was decreased in demented versus nondemented subjects, regardless of pathology. Soluble Aβ42 was increased in both groups with AD pathology, demented or not, compared to no dementia/no AD pathology subjects. Groups did not differ in TrkB isoform levels or in levels of total soluble tau, individual tau isoforms, threonine-181 tau phosphorylation, or ratio of phosphorylated 3R-4R isoforms. In BA9, soluble Aβ42 correlated with Mini-Mental State Examination scores and with BDNF messenger RNA expression. Thus, soluble Aβ42 and BDNF, but not TrkB or soluble tau, correlate with dementia in the oldest-old.

Keywords: Alzheimer's disease; Amyloid-beta; BDNF; Human postmortem; Tau; TrkB.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Aging
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Brain / metabolism*
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cognition / physiology*
  • Female
  • Gene Expression
  • Humans
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Neuropsychological Tests
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Phosphorylation
  • Protein Isoforms
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • RNA, Messenger / metabolism
  • Receptor, trkB
  • tau Proteins / metabolism


  • Amyloid beta-Peptides
  • Brain-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • Peptide Fragments
  • Protein Isoforms
  • RNA, Messenger
  • amyloid beta-protein (1-42)
  • tau Proteins
  • BDNF protein, human
  • Protein-Tyrosine Kinases
  • Receptor, trkB
  • tropomyosin-related kinase-B, human