Translational gene mapping of cognitive decline

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

doi:10.1016/j.neurobiolaging.2006.11.008

« Previous Next »Neurobiology of Aging
Volume 29, Issue 4 , Pages 524-541, April 2008

Translational gene mapping of cognitive decline

Beth Wilmot
- Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, OR, United States
- Corresponding author at: Department of Molecular and Medical Genetics, L103, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States. Tel.: +1 503 494 4362; fax: +1 503 494 7499.
Shannon K. McWeeney
- Division of Biostatistics, Department of Public Health and Preventive Medicine, Oregon Health and Sciences University, Portland, OR, United States
Randal R. Nixon
- Department of Pathology, Oregon Health and Sciences University, Portland, OR, United States
Thomas J. Montine
- Department of Pathology, University of Washington, Seattle, WA, United States
Jamie Laut
- Department of Neurology, Oregon Health and Sciences University, Portland, OR, United States
Christina A. Harrington
- Gene Microarray Shared Resource, Oregon Health and Sciences University, Portland, OR, United States
Jeffrey A. Kaye
- Department of Neurology, Oregon Health and Sciences University, Portland, OR, United States
Patricia L. Kramer
- Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, OR, United States
- Department of Neurology, Oregon Health and Sciences University, Portland, OR, United States

Received 25 April 2006; received in revised form 14 November 2006; accepted 16 November 2006. published online 16 December 2006.

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.

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