An etiological role of amyloidogenic carboxyl-terminal fragments of the beta-amyloid precursor protein in Alzheimer's disease.

Amyloid beta protein (A beta), 39-43 amino acids long, is the principal constituent of the extracellular amyloid deposits in brain that are characteristic of Alzheimer's disease (AD). Several lines of evidence indicate that A beta may play an important role in the pathogenesis of AD. However, there are several discrepancies between the production of A beta and the development of the disease. Thus, A beta may not be the sole active fragment of beta-amyloid precursor protein (betaAPP) in the neurotoxicity associated with AD. Consequently, the possible effects of other cleaved products of betaAPP need to be explored. The recent concentration on other potentially amyloidogenic products of betaAPP has produced interesting candidates, the most promising of which are the amyloidogenic carboxyl-terminal (CT) fragments of betaAPP. This review discusses a possible etiological role of CT fragments of betaAPP in AD.