Partial, Rather than Full, BACE1 Inhibition May Be a Better Therapeutic Strategy for Alzheimer’s Disease Due to Effects of Complete Loss of BACE1 Activity on Adult Hippocampal Neurogenesis

Complete loss of BACE1 activity increases NPC proliferation in the dentate gyrus. BrdU (green) and NeuN (red) coimmunofluoresence in the dentate gyrus of BACE1+/+, BACE1+/–, and BACE1–/– mice 1 d after BrdU injection. BACE1–/– mice exhibit significantly more BrdU+ cells compared to BACE1+/+ or BACE1+/– mice. Scale bar: 50 µm (adapted from Fig. 2A in Chatila et al., 2018).