When mice switch from producing APOE4 to APOE2 throughout their entire body, their blood shows a lipid profile similar to a rare human condition called type III hyperlipoproteinemia, with high triglycerides and ApoE, which could be a dangerous side effect if used as a therapy.
Evidence from Studies
No evidence studies found yet.
What Would Prove This
Per GRADE and EBM methodology, here is what ideal scientific evidence would look like to definitively prove or disprove this claim, ordered from strongest to weakest.
Whether systemic APOE2 expression in humans consistently leads to type III hyperlipoproteinemia and associated cardiovascular risks.
A systematic review and meta-analysis of all published human case reports and cohort studies of individuals with APOE2/E2 genotype, quantifying prevalence of hyperlipoproteinemia, plasma triglyceride levels, and cardiovascular events across diverse ancestries.
Whether systemic APOE4-to-APOE2 gene editing in humans increases plasma triglycerides and ApoE to levels associated with hyperlipoproteinemia.
A phase I RCT in 40 healthy APOE4/4 adults, randomized to receive systemic APOE4-to-APOE2 base editing via lipid nanoparticle or placebo, with primary outcomes of plasma triglycerides, ApoE concentration, and LDL/VLDL particle size measured at 1, 3, and 6 months.
Whether individuals with naturally occurring APOE2/E2 genotype develop hyperlipoproteinemia over time compared to APOE3/3 carriers.
A prospective cohort of 500 APOE2/E2 and 500 APOE3/3 adults aged 40–60, tracked for 10 years with annual lipid panels, liver function tests, and cardiovascular events, to assess incidence of type III hyperlipoproteinemia.
Whether individuals diagnosed with type III hyperlipoproteinemia are more likely to carry APOE2/E2 genotype than matched controls.
A case-control study of 200 individuals with confirmed type III hyperlipoproteinemia and 400 age- and sex-matched controls, genotyped for APOE to determine odds ratio of E2/E2 genotype in cases.
Whether individuals with APOE2/E2 genotype have higher plasma triglycerides and ApoE levels than APOE3/3 carriers at a single time point.
A cross-sectional analysis of 300 adults aged 45–65 with known APOE genotype, measuring fasting plasma triglycerides, ApoE concentration, and VLDL particle size, comparing E2/E2, E2/E3, and E3/E3 groups.