Cholesterol-independent neuroprotective and neurotoxic activities of statins: perspectives for statin use in Alzheimer disease and other age-related neurodegenerative disorders

Statins, long known to be beneficial in conditions where dyslipidemia occurs by lowering serum cholesterol levels, also have been proposed for use in neurodegenerative conditions, including Alzheimer disease. However, it is not clear that the purported effectiveness of statins in neurodegenerative disorders is directly related to cholesterol-lowering effects of these agents; rather, the pleiotropic functions of statins likely play critical roles. Moreover, it is becoming more apparent with additional studies that statins can have deleterious effects in preclinical studies and lack effectiveness in various recent clinical trials. This perspective paper outlines pros and cons of the use of statins in neurodegenerative disorders, with particular emphasis on Alzheimer disease.