1. The study examined the effects of genetically inhibiting β-site APP cleaving enzyme 1 (BACE1), which produces amyloid beta (Aβ), on functional outcomes after traumatic brain injury (TBI) in young adult mice. 2. The study found that BACE1 knockout mice performed worse on motor and cognitive tests after TBI compared to wild type mice. 3. The results suggest that further study is needed to evaluate therapies targeting BACE1-derived Aβ after TBI, as inhibition may not be beneficial across all age groups and injury severities.

1. Detrimental Effect of Genetic Inhibition of β-Site APP Cleaving Enzyme 1 on Functional Outcome after Controlled Cortical Impact In Young Adult Mice Rebekah Mannix M.D, MPH

3. From http://www.rndsystems.com/cb_detail_objectname_WI00_BaceAlzheimers.aspx

8. Relevance of Aβ across the spectrum of age? Roberts et al J Neurol Neurosurg Psychiatry, 1994 Control patients TBI patients

11. Is Bace1 derived Aβ a therapeutic target across the spectrum of age?

15. Results – Aβ 40 levels Sham vs. injured Bace1 +/+ mice (n= 6-11/group, p = 0.03) Sham vs. injured Bace1 -/- mice (n = 4-6/group, p=0.14)

16. Results - Wire Grip Injured Bace1 -/- compared to injured Bace1 +/+ (n=17-18/group p = 0.003)

17. Results – Morris Water Maze Bace 1 -/- mice performed significantly worse than sham-injured Bace 1 -/- mice (n= 6-8/group sham injury, 14-18 group CCI , p= 0.0029)

18. Results: Probe Trials Injured Bace1 -/- vs. Bace1 +/+ mice (p=0.0009)

19. Results n=8/group

22. Next Steps - Aβ rescue 200 pmol Aβ 40 ICV immediately after injury

25. Thank you