The Pathobiology of Alzheimer's Disease

Abstract

The discovery of β protein, the major component of the amyloid fibrils of the plaques and cerebral vessels and of the paired helical filaments of the neurofibrillary tangles, has provided a means to decipher the pathogenesis of Alzheimer's disease. The same lesions in aged Down's syndrome individuals have also been shown to be composed of β protein. Gene probes localize the gene for β protein, as well as that for familial Alzheimer's disease, to chromosome 21, but these genes are not linked. A study of posttranslational modifications of the 695-amino-acid β-protein gene precursor, with specific reference to abnormal proteolysis, may provide insights into the cause of the amyloidotic lesions of Alzheimer's disease and the means of arresting them.