Increased amyloid- levels in APPSWE transgenic mice treated chronically with a physiological high-fat high-cholesterol diet
Levin-Allerhand, J.A.; Lominska, C.E.; Smith, J.D.
Journal of Nutrition Health and Aging 6(5): 315-319
2002
ISSN/ISBN: 1279-7707 PMID: 12474021 Document Number: 542838
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.