Diet-induced hypercholesterolemia enhances brain A beta accumulation in transgenic mice.
Epidemiological data show correlations between hypercholesterolemia and Alzheimer's disease (AD). We test the hypothesis that hypercholesterolemia modulates Abeta deposition in mice overexpressing the human APP695 Swedish mutation (K670N and M671L) (TgAPPsw). Feeding mice a high fat/high cholesterol (HFHC) diet for 7-10 months increased total cholesterol levels by 4-fold. The extent of Abeta immunostained plaque-like deposits were significantly higher for mice fed the HFHC diet as compared with mice fed rodent chow. Extent of deposits correlated inversely with plasma levels of HDL and directly to apolipoprotein E. Overall, plasma lipoproteins may be an important factor in induction of AD-like plaques in mice. The lowering of plasma lipids may be therapeutic for AD patients.
Shie
Feng-Shiun
FS
Nutritional Sciences Interdisciplinary Program and Department of Pathology, Box 353410, Raitt Hall, Room 305, University of Washington, Seattle, WA 98195, USA.
Jin
Lee-Way
LW
Cook
David G
DG
Leverenz
James B
JB
LeBoeuf
Renée C
RC
D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D008074:Lipoproteins