Getting back to BACEics

Abstract

Alzheimer's Disease Drugs that block the β-secretase BACE1 are in clinical trials for treatment of Alzheimer's disease. However, their safety is unclear because mice lacking BACE1 exhibit neurological phenotypes. Ou-Yang et al. generated conditional BACE1 knockout mice in which the Bace1 gene was only ablated in the mature adult animal. Although these conditional adult BACE1 knockout mice largely lacked the phenotypes observed in germline knockout animals, they did exhibit a Bace1 -null phenotype—disorganization of an axonal pathway in the hippocampus, a brain region critical for memory. Thus, BACE1 inhibitors could potentially disturb hippocampal axonal pathways. Sci. Transl. Med. 10 , eaao5620 (2018).