Data from a number of epidemiological studies suggest that cholesterol levels might be related to risk for AD. In addition, data from a number of studies employing animal models of AD suggest that cholesterol modulates APP processing and consequently alters Aβ production and senile plaque deposition. Based on these lines of evidence, investigators, in this study, used the Tg2576 AD mouse model to explore the interaction between cholesterol and AD-like neuropathology. The authors separately examined the effects of lovastatin on cholesterol level on APP processing beta-amyloid production and senile plaque deposition, in male and female mice.Lovastatin lowered plasma cholesterol levels in both genders. The major findings of this study are:1) lovastatin lowered plasma cholesterol levels in both genders; 2) lovastatin enhanced the amounts of β-amyloid and other β-secretase derived peptides in females, but not in males;3) lovastatin increased the number of plaques in the hippocampus and cortex of females, but not in males; 4) lovastatin did not change the amounts of full-length or α-secretase processed APP or, PS1 in either sex. Thus, lovastatin lowers cholesterol level in both genders, but enhances β-amyloid production and senile plaque deposition only in brains of female Tg2576 mice. These results suggest that low cholesterol might be a risk factor for AD in females.