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

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 (Ab) and tau contribute to neurodegeneration. However, it is unknown whether AD-type neuropathology, soluble Ab 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 A beta 42 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 A beta 42 correlated with Mini-Mental State Examination scores and with BDNF messenger RNA expression. Thus, soluble A beta 42 and BDNF, but not TrkB or soluble tau, correlate with dementia in the oldest-old. (C) 2015 Elsevier Inc. All rights reserved.