High-fat-diet intake enhances cerebral amyloid angiopathy and cognitive impairment in a mouse model of alzheimer's disease, independently of metabolic disorders

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Abstract

© 2016 The Authors. Background--The high-fat Western diet is postulated to be associated with the onset and progression of Alzheimer's disease (AD). However, the role of high-fat-diet consumption in AD pathology is unknown. This study was undertaken to examine the role of highfat- diet intake in AD. Methods and Results--5XFAD mice, a useful mouse model of AD, and control wild-type mice were fed (1) high-fat diet or (2) control diet for 10 weeks. The effects on cerebral AD pathology, cognitive function, and metabolic parameters were compared between each group of mice. High-fat diet significantly enhanced cerebrovascular β-amyloid (Ab) deposition (P<0.05) and impaired cognitive function (P<0.05) in 5XFAD mice, but not in wild-type mice. High-fat diet enhanced hippocampal oxidative stress (P<0.05) and NADPH oxidase subunits, gp91phox (P<0.01) and p22phox (P<0.01) in 5XFAD mice, but not in wild-type mice. Furthermore, highfat diet reduced cerebral occludin (P<0.05) in 5XFAD mice, but not in wild-type mice. Thus, 5XFAD mice exhibited greater susceptibility to high-fat diet than wild-type mice regarding cerebrovascular injury and cognitive impairment. On the other hand, 5XFAD mice fed high-fat diet exhibited much less increase in body weight, white adipose tissue weight, and adipocyte size than their wild-type counterparts. High-fat diet significantly impaired glucose tolerance in wild-type mice but not in 5XFAD mice. Thus, 5XFAD mice had much less susceptibility to high-fat-diet-induced metabolic disorders than wild-type mice.

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Lin, B., Hasegawa, Y., Takane, K., Koibuchi, N., Cao, C., & Kim-Mitsuyama, S. (2016). High-fat-diet intake enhances cerebral amyloid angiopathy and cognitive impairment in a mouse model of alzheimer’s disease, independently of metabolic disorders. Journal of the American Heart Association, 5(6). https://doi.org/10.1161/JAHA.115.003154

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