The application provides novel neuroactive fragments of human amyloid precursor protein (APP). The fragments include sequence from the Aβ region of APP but also extend upstream. The fragments are soluble in aqueous solution most bands are about 10 kDa and above and do not correspond with the expected molecular weight of a dimer or trimer. The fragments and subfragments thereof can be used as immunogens in methods of immunotherapy to treat Alzheimer's and other amyloidogenic diseases characterized by deposits of Aβ in the brain. Antibodies to the part of the fragment upstream from APP or the interface between Aβ and the upstream sequence can also be used in such therapeutic method. The fragments are also useful as markers, which can be detected for diagnosis or prognosis of disease or for screening agents.