apoE isoforms and measures of anxiety in probable AD patients and Apoe ^-/- mice

Increased anxiety may occur in up to 70% of AD patients during the course of their illness. Here we show that human apoE isoforms, which differ in AD risk, have differential effects on measures of anxiety in adult Apoe ^-/- male mice expressing human apoE3 or apoE4 in their brains and male probable AD (PRAD) patients. Compared with wild-type mice, Apoe ^-/- mice without human apoE or with apoE4, but not apoE3, showed increased measures of anxiety. These behavioral alterations were associated with reduced microtubule-associated protein 2-positive neuronal dendrites in the central nucleus of the amygdala. Consistent with the mouse data, male and female PRAD patients with ε4/ε4 showed higher anxiety scores than those with ε3/ε3. We conclude that human apoE isoforms have differential effects on measures of anxiety.