THE NONAMYLOIDOGENIC P3 FRAGMENT (AMYLOID BETA-17-42) IS A MAJOR CONSTITUENT OF DOWNS-SYNDROME CEREBELLAR PREAMYLOID

Down's syndrome (DS) patients show accelerated Alzheimer's disease (AD ) neuropathology, which consists of preamyloid lesions followed by the development of neuritic plaques and neurofibrillary tangles. The majo r constituents of preamyloid and neuritic plaques are amyloid beta (A beta) peptides. Preamyloid lesions are defined as being A beta immunor eactive lesions, which unlike neuritic plaque amyloid are Congo red-ne gative and largely nonfibrillar ultrastructurally. DS patients can dev elop extensive preamyloid deposits in the cerebellum, without neuritic plaques; hence, DS cerebellums are a source of relatively pure preamy loid. We biochemically characterized the composition of DS preamyloid and compared it to amyloid in the neuritic plaques and leptomeninges i n the same patients. We found that A beta 17-42 or p3 is a major A bet a peptide of DS cerebellar preamyloid. This 26-residue peptide is also present in low quantities in neuritic plaques. We suggest that preamy loid can now be defined biochemically as lesions in which a major AP p eptide is p3.