Aβ reduction in BACE1 heterozygous null 5XFAD mice is associated with transgenic APP level.

Background The β-secretase, BACE1, cleaves APP to initiate generation of the β-amyloid peptide, Aβ, that comprises amyloid plaques in Alzheimer’s disease (AD). Reducing BACE1 activity is an attractive therapeutic approach to AD, but complete inhibition of BACE1 could have mechanism-based side-effects as BACE1−/− mice show deficits in axon guidance, myelination, memory, and other neurological processes. Since BACE1+/− mice appear normal there is interest in determining whether 50% reduction in BACE1 is potentially effective in preventing or treating AD. APP transgenic mice heterozygous for BACE1 have decreased Aβ but the extent of reduction varies greatly from study to study. Here we assess the effects of 50% BACE1 reduction on the widely used 5XFAD mouse model of AD.