SORBS2, SH3RF3, AND NPHP1 MODIFY AGE AT ONSET IN CARRIERS OF THE G206A MUTATION IN PSEN1 WITH FAMILIAL ALZHEIMER'S DISEASE

Abstract

Background: Anxiety disorders affect 18% of Americans, and their managements remain to be a great challenge for the society. Aside from the anxiety disorders, there are many diseases, including Alzheimer’s disease (AD), that have anxiety as one of their clinic symptoms.Mechanistic and therapeutic studies of the anxiety disorders often begin at animal level, such as rodent. For the latter, the anxiety level is most commonly assessed by elevated plus maze (EPM). However, the existing anxiety assessment methods, including EPM, display limited sensitivity, often due to very high in-group variations. Thus a more sensitive method is needed for better assessing animal anxiety. Methods: We created a novel elevated platform (EP) with open edges. The platform was divided into three consecutive concentric ring zones so that the anxiety challenge increased in a continuous gradient from the central zone towards the outer zone. For comparisons, the anxiety levels of APPsw (Tg2576) mice and GRK5 +/mice were assessed with open field (OF), EPM and the new EP.Results:Neither the OF, nor the EPM was able to reveal significant difference between any groups, but the EP did discover that APPsw mice displayed statistically significant higher anxiety level than the wild type controls.Conclusions: The EP is more sensitive than the OF and EPM in assessing the animal anxiety.