HealthDay News — Sustained and increasing BACE1 inhibition can reverse amyloid deposition in a mouse model of Alzheimer disease (AD), according to a study published in the Journal of Experimental Medicine.
Noting that BACE1 initiates the generation of the β-amyloid peptide, Xiangyou Hu, PhD, from the Cleveland Clinic, and colleagues generated conditional knockout BACE1fl/fl mice and bred them with ubiquitin-CreER mice to induce BACE1 deletion after early developmental stages.
The researchers found that amyloid deposition was completely reversed with sequential and increased deletion of BACE1 in an adult AD mouse model. Significant improvement in gliosis and neuritic dystrophy was seen with this reversal in amyloid deposition. In addition, there was significant improvement in synaptic functions, as determined by long-term potentiation and contextual fear conditioning experiments, in association with the reversal of amyloid plaques.
“Our results demonstrate that sustained and increasing BACE1 inhibition in adults can reverse amyloid deposition in an AD mouse model, and this observation will help to provide guidance for the proper use of BACE1 inhibitors in human patients,” the authors wrote.
Hu X, Das B, Hou H, He W, Yan R. BACE1 deletion in the adult mouse reverses preformed amyloid deposition and improves cognitive functions [published online February 14, 2018]. J Exp Med. doi:10.1084/jem.20171831