A noncompetitive BACE1 inhibitor TAK-070 ameliorates Abeta pathology and behavioral deficits in a mouse model of Alzheimer's disease

This study aimed at testing the non-peptidic, non-competitive BACE 1 inhibitor TAK-070 for efficacy in Tg 2576 mouse model of AD.  In Tg mice short-term oral administration of TAK-070 decreased the brain levels of soluble Abeta, increased levels of neurotrophic sAPP-alpha , and normalized the behavioral impairments in cognitive tests. Six month chronic treatment was found to ameliorate Abeta pathology (i.e., beta amyloid plaque load) and behavioral deficits in the Tg mice although the reduction in Abeta levels was deemed to be modest.  It is of note that   6 month chronic treatment with TAK-070 was well tolerated by Tg mice which survived comparable to mice treated with vehicle control. The authors concluded that  the successful treatment of  AD-like behavior and neuropathology in  a Tg AD model by a noncompetitive BACE1 inhibitor, TAK-070, provides strong support for the validity of partial BACE1 inhibition as a disease-modifying as well as symptomatic therapy for AD.