Study on A beta 34 biology and detection in transgenic mice brains

The beta -amyloid precursor protein undergoes cleavages by beta - and gamma -secretasses yielding amyloid- beta peptides (A beta ) that accumulate in Alzheimer's disease. Subsequently, A beta peptides are targets of additional truncations or endoproteolytic cleavages explaining the diversity of A beta -related fragments recovered in cell media or pathologic human fluids. Here, we focused on A beta 1-34 (A beta 34) that has been detected both in vitro and in vivo and that derives from the hydrolysis of A beta by beta -secretase. We have obtained and fully characterized by immunologic and biochemical approaches, a polyclonal antibody that specifically recognizes the C-terminus of A beta x-34. We present immunohistochemical evidence for the presence of A beta x-34 in the brain of 3xTg mice and Alzheimer's disease-affected human brains. Finally, we demonstrate a neprilysin-mediated degradation process of A beta 34 and the ability of synthetic A beta 34 to protect HEK cells overexpressing either wild type or Swedish-mutated beta -amyloid precursor protein from apoptosis.