2004 Investigator-Initiated Research Grant

Studies have shown that long-term use of cholesterol-lowering drugs called statins is associated with a decreased risk of developing Alzheimer’s. Investigations of statin treatment in mice with an Alzheimer-like disorder results in lower levels of beta-amyloid, the tiny protein fragment that is a key suspect in Alzheimer pathology.

Research on statins is inconclusive and has not explained exactly how the drugs might function as Alzheimer treatments. The effort to explain their effect is complicated by differences in how various versions of the drug operate. Some statins cannot cross the blood-brain barrier, the brain’s defense against foreign substances, but some statins can. Nonetheless, both kinds of statins have been linked to decreased beta-amyloid levels in mice.

Mark P. Burns, Ph.D., and colleagues are testing the hypothesis that there are two mechanisms of action by which statins affect beta-amyloid production. The statins that cross the barrier may directly inhibit the work of enzymes involved in beta-amyloid production. The statins that operate outside the brain may indirectly decrease cholesterol concentrations in brain cell membranes and, subsequently, alter the environment in which beta-amyloid is produced.

The research team will study in “Alzheimer” mice the function of two statins that cross the blood-brain barrier and of one that does not. The outcome of this work may clarify the therapeutic role of statins, demonstrate their potential as an intervention to treat or prevent Alzheimer’s, and help characterize the role of cholesterol in disease processes.