The beta-amyloid precursor protein undergoes cleavages by beta- and gamma-secretasses yielding amyloid-beta peptides (Abeta) that accumulate in Alzheimer's disease. Subsequently, Abeta peptides are targets of additional truncations or endoproteolytic cleavages explaining the diversity of Abeta-related fragments recovered in cell media or pathologic human fluids. Here, we focused on Abeta1-34 (Abeta34) that has been detected both in vitro and in vivo and that derives from the hydrolysis of Abeta by beta-secretase. We have obtained and fully characterized by immunologic and biochemical approaches, a polyclonal antibody that specifically recognizes the C-terminus of Abetax-34. We present immunohistochemical evidence for the presence of Abetax-34 in the brain of 3xTg mice and Alzheimer's disease-affected human brains. Finally, we demonstrate a neprilysin-mediated degradation process of Abeta34 and the ability of synthetic Abeta34 to protect HEK cells overexpressing either wild type or Swedish-mutated beta-amyloid precursor protein from apoptosis.