Apolipoprotein E and anxiety

Apolipoprotein E4 is a risk factor for developing Alzheimer's disease (AD) at an earlier age. Anxiety is most common in AD patients with an age-at-onset under 65 years old. We hypothesize that differential effects of human ApoE isoforms on anxiety contribute to this effect. We also hypothesize that these effects involve reduced synaptic histamine levels and reduced histamine receptor-mediated signaling in the amygdala. Rodent and human data supporting these hypotheses will be reviewed. Understanding how ApoE modulates measures of anxiety might help in the development of therapeutic targets to reduce or even prevent measures of anxiety in health and in dementing illnesses.