Beneficial effect of amyloid beta after controlled cortical impact

Background: Worse functional outcomes after controlled cortical impact (CCI) in Bace1(-/-) mice have previously been demonstrated. This study investigated whether reconstitution of amyloid-beta (A beta) after CCI in Bace1(-/-) animals would reverse the detrimental effect of Bace1 deletion. Methods: Bace1(-/-) and wild type Bace1(+/+) (C57Bl/ 6) mice were subjected to CCI (n = 14-23/ group) or sham injury (n= 6/ group). After injury, mice underwent intracerebroventricular injections of A beta(40) (n=23 Bace1(-/-) and 17 Bace1(+/+) per group) or vehicle (n=14 Bace1(-/-) and 22 Bace1(+/+) per group). Functional outcomes were assessed with wire grip (motor) and Morris water maze (spatial memory). Soluble A beta levels were assessed at 24 hours and 21 days after CCI. Lesion volume was assessed 21 days after injury. Results: At 24 hours after injury, A beta-treated Bace1(-/-) mice had A beta(40) levels similar to vehicle-treated Bace1(+/+) mice, but by 21 days after injury there were no differences between A beta-treated versus vehicle-treated Bace1(-/-) mice. Reconstitution with A beta(40) improved motor but not spatial memory or histopathological outcome in injured Bace1(-/-) mice. In contrast, treatment with A beta(40) worsened motor performance in Bace1(+/+) mice. Conclusions: The data suggest A beta(40) may have some beneficial effects after CCI in young adult mice and that therapies targeting BACE should be approached cautiously.