Increased expression of Abeta degrading enzyme IDE in the cortex of transgenic mice with Alzheimer's disease-like neuropathology.

Expression levels of amyloid beta (Abeta)-degrading enzymes, insulin degrading enzyme (IDE) and neprilysin (NEP), were examined in transgenic mice with Alzheimer's disease-like neuropathology. After the development of first Abeta plaques in transgenic mice brain, cortical mRNA and protein levels of IDE were significantly up-regulated in the transgenic mice compared to their non-transgenic littermates. Up-regulation of IDE mRNA-levels occurred in parallel with increased Abeta40 and Abeta42 production. Additionally, a significant positive correlation was observed between protein levels of IDE and full-length amyloid precursor protein (APP) in the cerebral cortex. mRNA and protein levels of NEP were also nominally up-regulated in Tg mice compared to controls. These data may reflect up-regulation of the IDE and possibly of NEP expression in response to the Abeta accumulation.