Neurochemical Research

, Volume 29, Issue 6, pp 1287–1297

Gene Expression Profiling in Fetal, Aged, and Alzheimer Hippocampus: A Continuum of Stress-Related Signaling

Article

DOI: 10.1023/B:NERE.0000023615.89699.63

Cite this article as:
Lukiw, W.J. Neurochem Res (2004) 29: 1287. doi:10.1023/B:NERE.0000023615.89699.63

Abstract

While specific components of normal brain aging and Alzheimer's disease (AD) appear to be genetically determined, it is not well understood whether AD is due to accelerated aging or if AD represents an independent disease entity superimposed upon senescence. Using gene expression profiling, significant alterations in brain-specific transcription patterns have been observed between AD and age-matched controls. In AD, although a general depression in brain genetic output has been reported, there are robust increases in the expression of potentially neuropathological genes. The data in this study show increases in the RNA abundance patterns for a stress-response, proinflammatory, apoptotic, and angiogenic gene family that occur during the transition from fetal to aged, and again during the transformation from aged to AD brain. Significantly up-regulated RNAs include those encoding stress-induced factors (HSP70), transcriptional repressors (DAXX), pentraxins (SAP), proapoptosis factors (FAS and DAXX), and several inflammatory markers (βAPP, CEX1, NF-IL6, NF-kappaBp100, cyclooxygenase-2, IL-1α and IL-1β precursors and cPLA2). These findings support the hypothesis that there is a continuum of stress-related gene expression as the brain ages and an advancement of inflammatory, apoptotic, and angiogenic gene signaling that correlates with the transition to AD.

AgingAlzheimer's diseaseangiogenesisbrain transcriptionhippocampusneuroinflammationpentraxincellular phospholipase A2

Copyright information

© Plenum Publishing Corporation 2004

Authors and Affiliations

  1. 1.LSU Neuroscience Center and Department of OphthalmologyLouisiana State University Health Sciences CenterNew Orleans