Amyloid beta protein and the basis for Alzheimer's disease.

The amyloid fibril protein isolated from the cerebrovascular amyloid deposits seen in 92% of cases of Alzheimer's disease and 100% of cases of Down's syndrome over the age of 40 has been shown to have a previously unknown amino acid sequence. This protein has been designated beta protein (beta P) and the type amyloid fibrils, ACv beta. Polyclonal and monoclonal antibodies raised to a synthetic peptide comprising the first 10 amino acids of beta P localized both to cerebrovascular amyloid deposits as well as to the amyloid cores of all "senile" plaques. An amino acid sequence analysis based on that of the beta P has been reported indicating that the plaque amyloid fibril deposits are also composed of beta P. These deposits must cause severe disruption of neuronal fibers. Thus beta P in the form of amyloid deposits seems intrinsic to the destruction of neuronal competence and thus to the ensuing dementia of Alzheimer's disease. Since proteolysis converts the beta P precursor (Pre beta P) into amyloid fibrils, it is possible that 1) an abnormality in synthesis of the Pre beta P, perhaps during post-transitional events, or 2) an abnormality in proteolytic processing occurs to afford beta P deposits and the pathologic changes in Alzheimer's disease. Regardless of the processing abnormality, beta P represents a major component in the pathogenesis of Alzheimer's disease.