SECRETORY CLEAVAGE SITE OF ALZHEIMER AMYLOID PRECURSOR PROTEIN IS HETEROGENEOUS IN DOWNS-SYNDROME BRAIN

alpha beta (beta/A4) is the major constituent of brain amyloid in Alzh eimer's disease (AD), Down's syndrome (DS) and normal aged persons. Th is protein is presumably derived by normal proteolysis from a precurso r protein (APP). In this study, C-terminal fragments of APP in a Tris/ Triton soluble fraction were partially purified from DS brain by hepar in-affinity and reverse phase chromatography, and analyzed by N-termin al amino acid sequencing after SDS polyacrylamide gel electrophoresis and Western blotting. We found at least six different C-terminal fragm ents including those with the entire AB region. These results suggest that secretory processing of APP is heterogeneous and generates amyloi dogenic C-terminal fragments.