Amyloid Beta sharply increases HMG-CoA reductase protein levels in astrocytes isolated from C57BL/6 mice

Introduction: It is believed that the accumulation of Amyloid Beta (A beta) and brain cholesterol are involved in Alzheimer's pathophysiology. Consequently, regulation of brain cholesterol is greatly important. In astrocytes, like other cells, HMG-CoA reductase plays a key role in the maintenance of normal cholesterol level. In this study expression and protein levels of HMG-CoA reductase is assessed in the presence and absence of A beta in mouse astrocytes. Methods: Mouse astrocytes were cultured and treated with A beta for 24 h. Protein expression of HMG-COA reductase was detected using western blotting. Moreover, real-time PCR was executed to determine the alterations in the HMG-COA reductase expression. Results: Statistical analysis of results showed that the protein levels of HMG-COA reductase in treated group with A beta has increased by 4-fold, while no significant changes was observed in the mRNA of the HMG-COA reductase gene compared to the control group. Conclusion: Our findings showed that A beta can sharply increase protein level of HMG-COA reductase which can potentially increase cholesterol synthesis. Therefore, A beta may somehow increase HMG-COA reductase stability which could be resulted in excessive cholesterol build-up and in the other side increasing of cholesterol leads to an increase in A beta deposition. We showed a new insights on the interplay between A beta and HMG-COA reductase which may be a scientific and reasonable explanation for over accumulation of cholesterol in Alzheimer's disease.