Abstract
The human apolipoprotein E isoforms, apoE2, apoE3, and apoE4, have differential effects on brain function. Compared to apoE3, apoE4 increases the risk of age-related cognitive decline in humans and female mice expressing apoE in neurons. Here, we show impaired spatial memory retention in female mice expressing apoE4 in astrocytes compared to those expressing apoE3 in astrocytes or lacking apoE. Thus, apoE4 impairs cognition whether expressed in neurons or astrocytes.