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University of British Columbia Hospital

Cheryl Wellington, PhD | BC, Canada

University of British Columbia Hospital

Cheryl Wellington, PhD | BC, Canada

The therapeutic potential of ABCA1 and apoE for Alzheimer's Disease

Alzheimer's Disease (AD) is a devastating illness that affects half of the population over 85 years of age. The brains of AD patients accumulate amyloid plaques, which are composed mainly of a toxic peptide called Aβ. Recent research has shown that cholesterol, a type of fat, plays a major role in AD, particularly in the formation or removal of amyloid plaques. My laboratory studies genes that control cholesterol in the brain and how they affect AD. One such gene is called ABCA1, and is known to be involved in cholesterol transport. Because cholesterol is a fat, it separates from water and does not move well in the watery bloodstream. ABCA1 is a protein that moves cholesterol onto carrier proteins called apolipoproteins, which can then transport cholesterol through the bloodstream. We have shown that mice that lack ABCA1 have a number of defects in brain cholesterol transport that involve apolipoprotein E (apoE), which is the major cholesterol carrier in the brain and a very well known risk factor for AD. Mice that lack ABCA1 are unable to produce normal amounts of apoE, and the little apoE that remains does not transport cholesterol well. Together, these defects lead to more amyloid in the brains of ABCA1-deficient mice. We have also shown that mice with excess ABCA1 have absolutely no amyloid in their brains. These studies demonstrate that ABCA1 is a key factor in AD. In this proposal, we propose to learn more how about ABCA1 affects apoE function to affect amyloid levels, and we will begin to determine whether drugs that increase ABCA1 can protect from AD.