BACE1 deletion in the adult mouse reverses preformed amyloid deposition and improves cognitive functions.

ABSTRACT: BACE1 initiates the generation of the β-amyloid peptide, which likely causes Alzheimer's disease (AD) when accumulated abnormally. BACE1 inhibitory drugs are currently being developed to treat AD patients. To mimic BACE1 inhibition in adults, we generated BACE1 conditional knockout (BACE1^fl/fl) mice and bred BACE1^fl/fl mice with ubiquitin-Cre^ER mice to induce deletion of BACE1 after passing early developmental stages. Strikingly, sequential and increased deletion of BACE1 in an adult AD mouse model (5xFAD) was capable of completely reversing amyloid deposition. This reversal in amyloid deposition also resulted in significant improvement in gliosis and neuritic dystrophy. Moreover, synaptic functions, as determined by long-term potentiation and contextual fe

SUBMITTER: Hu X 

PROVIDER: S-EPMC5839766 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature