The pathobiology of Alzheimer's disease.

The discovery of beta 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 beta protein. Gene probes localize the gene for beta 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 beta-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.