A beta PP Accumulation and/or Intraneuronal Amyloid-beta Accumulation? The 3xTg-AD Mouse Model Revisited

Abstract

The triple-transgenic Alzheimer's disease (AD) mouse model, 3xTg-AD, played an important role in supporting the intraneuronal amyloid-beta(A beta) hypothesis in AD. However, recent evidence claims that the 3xTg-AD mice accumulate amyloid-beta protein precursor (A beta PP) instead of A beta within neurons. In the present report, we re-investigated the 3xTg-AD mouse model and confirmed recent findings of age-dependent A beta PP accumulations. In addition, intraneuronal A beta was detected mainly in the neocortex using conformation-specific as well as antibodies directed against A beta neo-epitopes. In contrast to previous work, however, only minor levels of intraneuronal A beta were detected in the CA1 region of the hippocampus in aged 3xTg-AD mice.