Response to Schmidt et al.: Lower activity of cholesteryl ester transfer protein (CETP) and the risk of dementia: a Mendelian randomization analysis

Abstract

A recent paper concluded that cholesteryl ester transfer protein (CETP) inhibition may be a viable target to treat dementia, based on human genetic evidence of a protective effect of target inhibition on risk of Lewy body and Parkinson's dementia. Alzheimer's disease, which is by far the most prevalent cause of dementia (around 80% of all dementia cases) was not included as an outcome. Evidence shows CETP inhibition is unlikely to affect Alzheimer's risk and may even potentially modestly increase risk. There is also little evidence to support an effect of CETP inhibition on all-cause or vascular dementia. Thus, CETP inhibition is unlikely to be a viable target to treat the most prevalent causes of dementia.

Keywords: Alzheimer’s disease; CETP; Cholesteryl Ester transfer protein; Dementia; Drug target; Mendelian randomization; Vascular dementia.