Increased amyloid-  levels in APPSWE transgenic mice treated chronically with a physiological high-fat high-cholesterol diet.
Although plasma cholesterol levels are not generally associated with Alzheimer disease (AD) incidence, in vitro studies have found that increased cellular cholesterol levels are associated with increases in  -amyloid (A ) production, with a concomitant decrease in sAPPa, the secreted non amyloidogenic fragment of the amyloid precursor protein (APP). In two previous studies using a mouse model for AD-like pathology, non-physiological high-cholesterol diet has been shown to increase plasma and cerebral cholesterol levels, but have resulted in conflicting results on cerebral A  levels. In the present study APPSWE male transgenic mice were fed either a chow diet or a physiological high-fat high-cholesterol Western-type diet until the mice reached 1 year of age. Mice fed the Western type diet, compared to the low-fat chow diet, had increased body weight, plasma and cerebral cholesterol levels, as well as a 50% increase in cerebral A  levels. Cerebral levels of total APP were not altered while cerebral apoE levels were increased in the mice fed the Western-type diet, versus the chow-fed mice. These data demonstrate that chronic intake of a non-toxic high-cholesterol diet, which is similar to a human diet in fat and cholesterol content, was effective in increasing A  levels and further suggests that dietary cholesterol and/or fat may be a risk factor for AD.
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Jonathan D. Smith Ph.D., The Cleveland Clinic Foundation NC10, 2500 Euclid Avenue, Cleveland, OH 44195, USA. E-mail: smithj@lerner.cct.org
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