Evidence for the accumulation of Abeta immunoreactive material in the human brain and in transgenic animal models

In this review we highlight the evidence for an intracellular origin of Abeta (A(3) amyloid peptides as well as the observations for a pathological accumulation of these peptides in Alzheimer's disease and Down syndrome, as well as in transgenic animal models. We deliberate on the controversy as to whether the intracellular A beta immunoreactive material is simply an accumulation of unprocessed full length amyloid precursor protein (APP) or a mix of processed APP fragments including A beta. Finally, we discuss the possible pathological significance of these intracellular APP fragments and the expected future research directions regarding this thought-provoking problem. (C) 2012 Elsevier Inc. All rights reserved.