Secretory cleavage site of Alzheimer amyloid precursor protein is heterogeneous in Down's syndrome brain

FEBS Letters

Tokuda, Takahiko²  Kametania, Fuyuki²  Ikeda, Shu-ichi¹  Tanaka, Kikuko² 

[1] Department of Medicine (Neurology), Shinshu University School of Medicine, Matsumoto 390, Japan;Department of Molecular Biology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156, Japan

关键词: Alzheimer's disease;    Down's syndrome;    Amyloid β protein precursor;    Aβ;   

DOI  :  10.1016/0014-5793(94)00851-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Aβ (β/A4) is the major constituent of brain amyloid in Alzheimer's disease (AD), Down's syndrome (DS) and normal aged persons. This protein is presumably derived by normal proteolysis from a precursor protein (APP). In this study, C-terminal fragments of APP in a Tris/Triton soluble fraction were partially purified from DS brain by heparin-affinity and reverse phase chromatography, and analyzed by N-terminal amino acid sequencing after SDS polyacrylamide gel electrophoresis and Western blotting. We found at least six different C-terminal fragments including those with the entire Aβ region. These results suggest that secretory processing of APP is heterogeneous and generates amyloidogenic C-terminal fragments.

【 授权许可】

Unknown