Therapeutic potential of statins in Alzheimer's disease.
There is increasing evidence linking cholesterol metabolism with the neurofibrillary pathology of Alzheimer's disease (AD). Cholesterol and its transport have been shown to be involved in the regulation of amyloid production and tau hyperphosphorylation in the brain, while also contributing to intracranial vascular disease and cerebral ischemia. Statins inhibit HMG-CoA reductase, the enzyme that catalyzes the rate-limiting step in cholesterol biosynthesis thus inserting itself into the pathogenesis of AD. Numerous studies have examined the role of statins in the prevention of dementia and treatment of established AD. This paper describes the role of cholesterol in the pathogenesis of AD and explores how statins may influence this balance. A review of the epidemiological and clinical trials with statins in dementia and AD is also presented. While evidence from retrospective case control studies suggests a beneficial role of statins in the prevention of AD, a similar benefit has not been established in prospective cohort studies or clinical trials. The ability of statins in protecting against AD is not yet elucidated. In the near future recently completed but not yet reported randomized clinical trials will hopefully clarify the role of statins in the treatment of AD.
Kandiah
Nagaendran
N
Division of Neurology, University of British Columbia, Canada.
Feldman
Howard H
HH