Mice carrying APOE2 alongside APOE4 showed less of some amyloid-related brain changes than mice carrying APOE3 alongside APOE4. The newly published peer-reviewed experiment examines how versions of a human Alzheimer’s risk gene interact in an amyloid-prone model. Effects differed across brain and blood measurements, and the findings do not establish cognitive improvement or a treatment for people.
APOE2 attenuated several APOE4-associated amyloid changes in a peer-reviewed mouse experiment. APOE is a human gene associated with Alzheimer’s risk. Kai Chen and colleagues compared mice carrying different pairs of its versions, including APOE2/4 and APOE3/4, against an APOE3/3 control group. The animals incorporated the amyloid-prone 5xFAD model and were examined at 10 months.[1]
Plaques form when the protein fragment amyloid beta accumulates outside cells. APOE3/4 mice had greater deposition and reduced interaction between plaques and microglia, the brain’s immune cells. Some of these changes were attenuated in APOE2/4 mice. Their broader brain protein profile also more closely resembled the comparison groups.[1]
The response varied across measurements. A protein associated with nerve-fibre insulation increased in APOE2/3 mice but not APOE2/4 mice. Some blood cholesterol-ester changes were similar in APOE3/4 and APOE2/4 animals. Vascular markers showed no significant differences among groups.[1]
The experiment cannot conclusively distinguish protection by APOE2 from reduced APOE4-associated activity. Cell-specific experiments are needed to identify the populations mediating the interaction. The amyloid findings concern this animal model; the measurements provide no assessment of people’s cognition or response to treatment.[1]
