Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer's disease

Nicole C. Berchtold, Paul Coleman, David H. Cribbs, Joseph Rogers, Daniel L. Gillen, Carl W. Cotman

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Synapses are essential for transmitting, processing, and storing information, all of which decline in aging and Alzheimer's disease (AD). Because synapse loss only partially accounts for the cognitive declines seen in aging and AD, we hypothesized that existing synapses might undergo molecular changes that reduce their functional capacity. Microarrays were used to evaluate expression profiles of 340 synaptic genes in aging (20-99 years) and AD across 4 brain regions from 81 cases. The analysis revealed an unexpectedly large number of significant expression changes in synapse-related genes in aging, with many undergoing progressive downregulation across aging and AD. Functional classification of the genes showing altered expression revealed that multiple aspects of synaptic function are affected, notably synaptic vesicle trafficking and release, neurotransmitter receptors and receptor trafficking, postsynaptic density scaffolding, cell adhesion regulating synaptic stability, and neuromodulatory systems. The widespread declines in synaptic gene expression in normal aging suggests that function of existing synapses might be impaired, and that a common set of synaptic genes are vulnerable to change in aging and AD.

Original languageEnglish (US)
Pages (from-to)1653-1661
Number of pages9
JournalNeurobiology of Aging
Volume34
Issue number6
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

Fingerprint

Synapses
Alzheimer Disease
Down-Regulation
Brain
Genes
Post-Synaptic Density
Neurotransmitter Receptor
Synaptic Vesicles
Automatic Data Processing
Cell Adhesion
Gene Expression

Keywords

  • Cortex
  • Limbic
  • Microarray
  • Molecular reprogramming
  • Neurotransmitter receptors
  • Scaffolding molecules
  • Synaptic vesicle trafficking

ASJC Scopus subject areas

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

Cite this

Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer's disease. / Berchtold, Nicole C.; Coleman, Paul; Cribbs, David H.; Rogers, Joseph; Gillen, Daniel L.; Cotman, Carl W.

In: Neurobiology of Aging, Vol. 34, No. 6, 01.06.2013, p. 1653-1661.

Research output: Contribution to journalArticle

Berchtold, Nicole C. ; Coleman, Paul ; Cribbs, David H. ; Rogers, Joseph ; Gillen, Daniel L. ; Cotman, Carl W. / Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer's disease. In: Neurobiology of Aging. 2013 ; Vol. 34, No. 6. pp. 1653-1661.
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