Fig.3.

Single injection (30μg) of an AβO-specific antibody ameliorates cognitive deficits in AD mice for at least 40 days. 5xFAD Tg mice and their wild-type (WT) littermates (6 months of age) were evaluated by Object Recognition Tasks before and after (40 days) a single injection (30μg) of a humanized AβO-specific antibody (anti-AβO) or non-specific human IgG (hIgG). First, locomotor activity was assessed while mice were allowed to habituate to the testing field (Habituation). Assessments were the number of times the mice crossed grids in the field (Crossings, light gray) and the number of times mice put their hind paws on the walls of the field (Rearings, purple), with no differences between WT and 5xFAD mice. Next, the test objects (F1 and F2) were introduced to the mice in the Training session. All mice showed normal exploratory behavior, defined by 50% exploration of each object, as both objects are equal and new to the mice. The ability of mice to remember object placement was then tested 24 hours after the Training session in a hippocampal (HP)-dependent task. Another 24 hours later, the ability of mice to remember the object was tested in a cortical (CT)-dependent task. Only the WT mice were able to recognize the familiar object (F1) from the Training session, as evidenced by >50% exploration of the displaced (D, pink) or new (N, light blue) object. The 5xFAD mice failed to recognize F1 in both tasks. When re-evaluated 40 days post-antibody injection in a HP-dependent task, only the 5xFAD mice that received the AβO antibody recovered their ability to recognize object F1. These data support the hypothesis that AβOs induce memory dysfunction in AD (Bicca and Klein, unpublished).