Diet-induced hypercholesterolemia enhances brain Aβ accumulation in transgenic mice

Epidemiological data show correlations between hypercholesterolemia and Alzheimer's disease (AD). We test the hypothesis that hypercholesterolemia modulates Aβ 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 Aβ 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.