Increased expression of TrkB and Capzb2 accompanies preserved cognitive status in early alzheimer disease pathology

Patricia F. Kao, Meredith G. Banigan, Charles R. Vanderburg, Ann C. McKee, Peter R. Polgar, Sudha Seshadri, Ivana Delalle

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) may influence brain reserve, the ability of the brain to tolerate pathological changes without significant decline in function. Here, we explore whether a specifically vulnerable population of human neurons shows a compensatory response to the neuropathological changes of Alzheimer disease (AD) and whether that response depends on an upregulation of the BDNF pathway. We observed increased neuronal TrkB expression associated with early-stage AD pathology (Braak and Braak stages I-II) in hippocampal CA1 region samples from cognitively intact Framingham Heart Study subjects (n = 5) when compared with cognitively intact individuals with no neurofibrillary tangles (n = 4). Because BDNF/TrkB signaling affects memory formation and retention through modification of the actin cytoskeleton, we examined the expression of actin capping protein β2 (Capzb2), a marker of actin cytoskeleton reorganization. Capzb2 expression was also significantly increased in CA1 hippocampal neurons of cognitively intact subjects with early-stage AD pathology. Our data suggest that increased expression of TrkB and Capzb2 accompanies adequate brain reserve in the initial stages of AD pathology. In subsequent stages of AD, the higher levels of TrkB and Capzb2 expression achieved may not be sufficient to prevent cognitive decline.

Original languageEnglish (US)
Pages (from-to)654-664
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume71
Issue number7
DOIs
StatePublished - Jul 1 2012
Externally publishedYes

Keywords

  • Alzheimer disease
  • Brain reserve
  • Brain-derived neurotrophic factor
  • Capzb2
  • TrkB

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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