Cholesterol metabolism, apolipoprotein E, adenosine... : Current Opinion in Lipidology (original) (raw)

Lipid metabolism

Cholesterol metabolism, apolipoprotein E, adenosine triphosphate-binding cassette transporters, and Alzheimer's disease

Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada

Correspondence to Cheryl L. Wellington, Department of Pathology and Laboratory Medicine, University of British Columbia, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4 Tel: +1 604 875 2000 (ext. 6825); fax: +1 604 875 3120; e-mail: [email protected]

Abstract

Purpose of review

Recent evidence suggests that cholesterol metabolism participates in the pathogenesis of Alzheimer's disease. Apolipoprotein E is the main lipid carrier in the brain and the best-established risk factor for late-onset Alzheimer's disease. Intracellular cholesterol levels influence the generation of amyloid-β peptides, the toxic species thought to be a primary cause of Alzheimer's disease. Finally, compounds that modulate cholesterol metabolism affect amyloid-β generation. This review summarizes data linking apolipoprotein E and adenosine triphosphate-binding cassette transporters to aspects of cholesterol metabolism and Alzheimer's disease pathogenesis.

Recent findings

In vivo, the lipidation status of apolipoprotein E affects amyloid-β burden in mice with Alzheimer's disease, which appears to caused by the modulation of amyloid-β deposition or clearance rather than amyloid-β production. State-of-the-art in-vivo assays reveal that amyloid-β is cleared from the brain by multiple pathways. Members of the adenosine triphosphate-binding cassette superfamily of transporters regulate lipid homeostasis and apolipoprotein metabolism in the brain, and may affect Alzheimer's disease pathogenesis by modulating apolipoprotein E lipidation as well as intracellular sterol homeostasis.

Summary

Proteins involved in brain cholesterol metabolism may affect the pathogenesis of Alzheimer's disease. Compounds that modulate the expression of these proteins may be of therapeutic benefit in Alzheimer's disease.