A CALCIUM-ACTIVATED PROTEASE FROM ALZHEIMERS-DISEASE BRAIN CLEAVES AT THE N-TERMINUS OF THE AMYLOID BETA-PROTEIN

Alzheimer's disease, Down's syndrome, and to a far lesser extent, normal aged brains exhibit abnormal extracellular deposits of amyloid. The major component of brain amyloid is the β-protein, a 4Kd fragment of the larger β-protein precursor. The finding of the abnormally processed β-protein and a protease inhibitor (α1-antichymotrypsin) in the amyloid deposits prompted us to search for proteases which may generate the β-protein from its precursor. We now report on the presence and partial purification of one such proteolytic activity from Alzheimer's brain. Normal physiologic C-terminal cleavage of the secreted form of the β-protein precursor occurs in the middle of the β-protein suggesting that the β-protein accumulates due to an alternative degradation pathway. We propose here that the protease activity we describe participates in this abnormal pathway. © 1991.