期刊
NEUROBIOLOGY OF AGING
卷 34, 期 6, 页码 1653-1661出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2012.11.024
关键词
Microarray; Synaptic vesicle trafficking; Neurotransmitter receptors; Scaffolding molecules; Cortex; Limbic; Molecular reprogramming
资金
- National Institute on Aging [R01 AG23173, AG34667, P50 AG16573, AG00538, RO1 AG36400, AG7367]
- Alzheimer Association [IIRG 91822]
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. Published by Elsevier Inc.
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