Reverse relationship between beta-amyloid precursor protein and beta-amyloid peptide plaques in Down's syndrome versus sporadic/familial Alzheimer's disease

Strong genetic evidence has been accumulated in favor of a central role of beta-amyloid precursor protein (APP) and beta-amyloid peptide (beta A4) in the pathogenesis of Alzheimer's disease (AD). We employed four newly develo ped APP and beta A4 antibodies and performed a comparative neuropathologica l study of patients with Down's syndrome (DS), early-onset familial AD and sporadic AD to investigate the distribution of APP and beta A4 plaque densi ties in the cerebral cortex of these disorders. Quantitative analysis of AP P versus beta A4 plaques revealed that brains with early-onset familial AD and sporadic AD showed significantly more beta A4 plaques than brains with DS (P < 0.05). In contrast, APP plaques were more abundant in DS cerebral c ortex (P < 0.02). These observations suggest that the development of pathol ogical changes in DS brains does not parallel that observed in AD, which mi ght be attributable to different causes in the pathogenesis of beta A4 form ation. A comparison of these disorders may be useful to further complement our knowledge of the mechanisms leading to plaque development.