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

Abstract Introduction It is believed that the accumulation of Amyloid Beta (Aβ) 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 Aβ in mouse astrocytes. Methods Mouse astrocytes were cultured and treated with Aβ for 24h. 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 Aβ 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 Aβ can sharply increase protein level of HMG-COA reductase which can potentially increase cholesterol synthesis. Therefore, Aβ 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 Aβ deposition. We showed a new insights on the interplay between Aβ and HMG-COA reductase which may be a scientific and reasonable explanation for over accumulation of cholesterol in Alzheimer's disease.