Effects of diet-induced hypercholesterolemia on amyloid accumulation in ovariectomized mice

Abstract

A central hypothesis in the study of Alzheimer's disease (AD) is the accumulation and aggregation of beta-amyloid peptide (A beta). Recent epidemiological studies suggest that patients with elevated cholesterol and decreased estrogen levels are more susceptible to AD through A beta accumulation. To test the above hypothesis, we used ovariectomized with diet-induced hypercholesterolemia (OVX) and hypercholesterolemia (HCL) diet alone mouse models. HPLC analysis reveals the presence of beta amyloid in the OVX and HCL mice brain. Congo red staining analysis revealed the extent of amyloid deposition in OVX and hypercholesterolemia mice brain. Overall, A beta levels were higher in OVX mice than in HCL. Secondly, estrogen receptors alpha (ER alpha) were assessed by immunohistochemistry and this suggested that there was a decreased expression of ER alpha in OVX animals when compared to hypercholesterolemic animals. A beta was quantified by Western blot and ELISA analysis. Overall, A beta levels were higher in OVX mice than in HCL mice. Our experimental results suggested that OVX animals were more susceptible to AD with significant increase in A beta peptide.