Bace2 Transgenic Models and Beta-Amyloid Modulation

Project Summary

Amyloid beta peptides are created by the activities of beta- and gamma-secretases, two enzymes that are required to cut amyloid precursor protein (APP). Two beta-secretases called BACE1 and BACE2 may be involved in the generation of the toxic amyloid beta proteins. Dr. Wong has bred mice that lack the BACE1 enzyme. He has found that neurons from the mice lacking BACE1 no longer produce amyloid beta peptides, and this suggests that BACE1 is the principal enzyme required to generate amyloid beta proteins. Studies from other laboratories also suggest that BACE2 may serve to limit the production of amyloid beta. To test this hypothesis, Dr. Wong is attempting to create mice that produce high amounts of normal and/or mutant BACE2 to determine if these genetic alterations curtail amyloid beta production in ways that are consistent with the hypothesis. BACE2 mice will also be bred with "AD" mice to determine if the accumulation of amyloid beta is curtailed by the production of high amounts of BACE2. If it is, this knowledge could pave the way for scientists to design and test drugs that increase the level of BACE2 activity in humans with AD.