Abstract
Background and PurposeCognitive impairment resulting from cerebrovascular insufficiency has been termed vascular cognitive impairment, and is generally accepted to be distinct from Alzheimer's disease resulting from a neurodegenerative process. However, it is clear that this simple dichotomy may need revision in light of the apparent occurrence of several shared features between Alzheimer's disease and vascular cognitive impairment. Nevertheless, it still remains largely unknown whether the burden of vascular- and Alzheimer-type neuropathology are independent or interdependent. Therefore, we investigated whether chronic cerebral hypoperfusion influences cognitive ability or amyloid β deposition in amyloid precursor protein (APP) overexpressing transgenic mice.MethodsTwo months old mice overexpressing a mutant form of the human APP bearing both the Swedish and Indiana mutations (APPSw/Ind-Tg mice), or their wild-type littermates, were subjected to chronic cerebral hypoperfusion with bilateral common carotid artery stenosis (BCAS) using microcoils or sham operation. Barnes maze test performance and histopathological findings were analyzed at eight months old by 2×2 factorial experimental designs with four groups.ResultsBCAS-operated APPSw/Ind-Tg mice showed significantly impaired learning ability compared to the other three groups of mice. Two-way repeated measures analysis of variance showed a synergistic interaction between the APP genotype and BCAS operation in inducing learning impairment. The cognitive performances were significantly correlated with the neuronal densities. BCAS significantly reduced the density of Nissl-stained neurons and silver-stained cored plaques in the hippocampus of APPSw/Ind-Tg mice but increased the amount of filter-trap amyloid β in the extracellular-enriched soluble brain fraction, compared to those from sham operated mice.ConclusionsThe results suggest interaction between chronic cerebral hypoperfusion and APPSw/Ind overexpression in cognitive decline in mice through enhanced neuronal loss and altered amyloid β metabolism.
Highlights
Insufficient blood supply to the brain has been shown to lead to cognitive dysfunction [1]
Two-way repeated measures analysis of variance showed a synergistic interaction between the amyloid precursor protein (APP) genotype and bilateral common carotid artery stenosis (BCAS) operation in inducing learning impairment
BCAS significantly reduced the density of Nissl-stained neurons and silver-stained cored plaques in the hippocampus of APPSw/Ind-Tg mice but increased the amount of filter-trap amyloid b in the extracellular-enriched soluble brain fraction, compared to those from sham operated mice
Summary
Insufficient blood supply to the brain has been shown to lead to cognitive dysfunction [1]. Cognitive impairment resulting from such cerebrovascular insufficiency has been termed ‘vascular cognitive impairment’ (VCI) [1], and is generally accepted to be distinct from Alzheimer’s disease (AD) resulting from a neurodegenerative process. Cognitive impairment resulting from cerebrovascular insufficiency has been termed vascular cognitive impairment, and is generally accepted to be distinct from Alzheimer’s disease resulting from a neurodegenerative process. It is clear that this simple dichotomy may need revision in light of the apparent occurrence of several shared features between Alzheimer’s disease and vascular cognitive impairment. It still remains largely unknown whether the burden of vascular- and Alzheimer-type neuropathology are independent or interdependent. We investigated whether chronic cerebral hypoperfusion influences cognitive ability or amyloid b deposition in amyloid precursor protein (APP) overexpressing transgenic mice
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