Translational gene mapping of cognitive decline

Beth Wilmot, Shannon K. McWeeney, Randal R. Nixon, Thomas J. Montine, Jamie Laut, Christina A. Harrington, Jeffrey A. Kaye, Patricia L. Kramer

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The ability to maintain cognitive function during aging is a complex process subject to genetic and environmental influences. Alzheimer's disease (AD) is the most common disorder causing cognitive decline among the elderly. Among those with AD, there is broad variation in the relationship between AD neuropathology and clinical manifestations of dementia. Differences in expression of genes involved in neural processing pathways may contribute to individual differences in maintenance of cognitive function. We performed whole genome expression profiling of RNA obtained from frontal cortex of clinically non-demented and AD subjects to identify genes associated with brain aging and cognitive decline. Genetic mapping information and biological function annotation were incorporated to highlight genes of particular interest. The candidate genes identified in this study were compared with those from two other studies in different tissues to identify common underlying transcriptional profiles. In addition to confirming sweeping transcriptomal differences documented in previous studies of cognitive decline, we present new evidence for up-regulation of actin-related processes and down-regulation of translation, RNA processing and localization, and vesicle-mediated transport in individuals with cognitive decline.

Original languageEnglish (US)
Pages (from-to)524-541
Number of pages18
JournalNeurobiology of Aging
Volume29
Issue number4
DOIs
StatePublished - Apr 1 2008

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Keywords

  • Alzheimer's disease
  • Cognitive decline
  • Cognitive reserve
  • Gene expression profiling
  • Healthy brain aging
  • Intersectin 1
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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