期刊
NEUROBIOLOGY OF AGING
卷 34, 期 3, 页码 679-693出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2012.06.025
关键词
Oligoemia; Cerebral ischemia; Vascular dysfunction; Cerebrovascular disease; Chronic cerebral hypoperfusion; Cerebral blood flow; Alzheimer's disease; Vascular risk factors
资金
- Canadian Institutes of Health Research (CIHR)
- Canadian Stroke Network (CSN)
- CSN
- European Stroke Network (ESN) Collaborative Research Initiative
Understanding the contribution of cerebrovascular factors in the progression of cognitive decline in Alzheimer's disease (AD) is a key step for the development of preventive therapies. Among these factors, chronic cerebral hypoperfusion is an early component of AD pathogenesis that can predict the progression from mild cognitive impairment to AD. Here, we investigated the effects of a protocol of mild chronic cerebral hypoperfusion in the APPswe/PS1 transgenic mouse model of AD. We observed that the permanent occlusion of the right common carotid artery induced spatial learning impairments in young APPswe/PS1 mice, but not in their wild type littermates. Furthermore, the extent of learning deficits strongly correlated with the number of cortical beta-amyloid plaques, with the mobilization of monocytes into the blood and with the number of bone marrow-derived microglia in the brain. These results indicate that a mild reduction of cerebral blood flow can selectively induce cognitive deficits at an early stage of amyloid pathology, eliciting a cellular innate immune response, even without causing neuronal death. (c) 2013 Elsevier Inc. All rights reserved.
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