Simvastatin and other HMG-CoA reductase inhibitors on brain cholesterol levels in Alzheimer's disease.
Alzheimer's 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 Alzheimer's 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 Alzheimer's and dementia has been translated into clinical setups. One of the most widely accepted theories of Alzheimer's 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 Alzheimer's disease research.
Department of Medicinal & Biological Chemistry, The University of Toledo College of Pharmacy, Toledo, Ohio 43614, USA.
Justin
J
Longenberger
Zahoor A
ZA
Shah
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D019821:Simvastatin / Q000627:therapeutic use*
D016229:Amyloid beta-Peptides; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D019821:Simvastatin