期刊
IBRO REPORTS
卷 4, 期 -, 页码 18-21出版社
ELSEVIER
DOI: 10.1016/j.ibror.2018.01.003
关键词
Amyloid precursor protein; Hippocampus; Neuroinflammation; Prevention; TgCRND8 mice; Tumor necrosis factor alpha; XPro1595
资金
- Canadian Institutes of Health Research [CIHR: 106649, 134059]
The characterization of preclinical stages of Alzheimers disease (AD) would provide a therapeutic window for prevention. One of the challenges of developing preventive therapy for AD is to identify early biomarkers for intervention studies. We have recently shown that in the TgCRND8 transgenic AD mouse model, increased hippocampal levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFa) and enhanced excitatory synaptic transmission were early-onset changes that occurred weeks before amyloid plaque formation. Inhibiting TNFa before plaque formation not only normalized excitatory synaptic function, but also prevented the impairment of synaptic function 4 months later. In this review paper, we will examine the potential contributions of TNFa to the alteration of brain function in preclinical AD. The prospective use of TNFa inhibitors for preventing AD will be discussed. (C)0 2018 The Authors. Published by Elsevier Ltd on behalf of International Brain Research Organization.
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