Simvastatin and Other HMG-CoA Reductase Inhibitors on Brain Cholesterol Levels in Alzheimers Disease

Justin      Longenberger; Zahoor      A. Shah

Abstract

Alzheimers disease, one of the most common forms of dementia, is a neurodegenerative disorder characterized by progressive cognitive decline and affects as many as 5.3 million people in United States alone. Both Alzheimers and dementia have tripled the cost of health care for elderly people, amounting to about $148 billion each year. Although there have been numerous drugs designed so far, no ideal or successful drug treatment for Alzheimers and dementia has been translated into clinical setups. One of the most widely accepted theories of Alzheimers pathology is the aggregation of amyloid-beta (Aβ) into extracellular cortical and hippocampal plaques. It has also been postulated that excessive cholesterol build-up in the brain plays an integral role in Aβ aggregation, and using HMG-coA reductase inhibitors may reduce Aβ accumulation by lowering brain cholesterol levels. Based on the success of animal studies and phase II clinical trials, HMG-coA reductase inhibitors may provide a viable alternative therapy in AD treatment. This review highlights the results of both pre-clinical and clinical trials on HMG-coA reductase inhibitors in order to give a comprehensive overview of their recent progress in Alzheimers disease research.

Keywords: Alzheimer's disease, cholesterol, HMG-coA reductase inhibitors, amyloid-beta, dementia, gemma-secretase, C-terminal fragment, glutamatergic function, L-DOPA