High cholesterol levels correlate with poor prognosis in conditions such as coronary heart disease and Alzheimer’s disease (AD).
But whether or not cholesterol is harmful also depends on where it goes within cells, and what it is bound to, report Dora Kovacs and her colleagues at Massachusetts General Hospital in Boston, USA (Nature Cell Biology, Vol 3, No 10, 01 Oct 01). For example, high levels of cholesteryl-ester occur with high levels of Amyloid-beta - a protein that ups the risk of developing AD, Kovacs’ team reports. While it is still unclear whether these aggregates are the direct cause of neurodegeneration, it has been reported that antibodies to Amyloid-beta can be used to vaccinate against AD.
Kovacs’ group find that inhibitors of the enzyme that drives the formation of cholesteryl-ester (acyl-coenzymeA:cholesterol acetyltransferase (ACAT)) lower Amyloid-beta levels, and could thus be used in the treatment of AD. These inhibitors could move to clinical trials quite quickly, as they have already been safety approved for the treatment of atherosclerosis.
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