Evacetrapib
Reducing CETP activity with evacetrapib preserves memory in an Alzheimer's mouse model, independent of amyloid or tau markers (EMBO Mol Med 2026)
Original title: Reducing CETP activity prevents memory decline in an Alzheimer's disease mouse model
Epidemiological studies link lower CETP activity to reduced Alzheimer's disease risk, but whether CETP inhibitors like evacetrapib, previously assessed only for cardiovascular disease, could affect Alzheimer's disease had not been tested. Using CETP transgenic mice crossed with an amyloidosis model and treated with evacetrapib, the authors found CETP inhibition maintained memory independent of classic Alzheimer's disease markers, an effect likely linked to preserved vascular health, alongside increased hippocampal cholesterol and altered plasma lipoproteins. Proteomic analysis of cerebrospinal fluid from cognitively unimpaired at-risk individuals in the PREVENT-AD cohort confirmed the mouse model reflects physiological changes already present in pre-symptomatic humans, supporting repurposing CETP inhibitors as a strategy to delay or prevent cognitive decline in Alzheimer's disease.
Original abstract
Epidemiological studies have shown that lower activity of the cholesteryl ester transfer protein (CETP) correlates with reduced Alzheimer's disease (AD) risk. While small-molecule CETP inhibitors like evacetrapib have previously been assessed for cardiovascular diseases, their involvement in AD has not been investigated. Here, we establish CETP as a novel pharmacological target for AD treatment. Using CETP transgenic mice crossed to a mouse model of amyloidosis and administering evacetrapib, we provide evidence that CETP inhibition maintained memory independent of classic AD markers, likely through maintained vascular health, while increasing hippocampal cholesterol and altering plasma lipoproteins. Using proteomic data of cerebrospinal fluid (CSF) from cognitively unimpaired individuals at risk for AD in the PResymptomatic EValuation of Experimental or Novel Treatments for AD (PREVENT-AD) cohort, we confirm that our mouse model reflects physiological changes in pre-symptomatic human subjects. We propose the repurposing of CETP inhibitors as an effective therapeutic strategy to delay or prevent cognitive impairment in AD.
cognitionevacetrapibmechanisms
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.