PROTEOLYTIC DEGRADATION OF MICROTUBULE-ASSOCIATED PROTEIN-TAU BY THROMBIN

Deposits in the brain of beta-amyloid and tau proteins constitute the two major characteristics of Alzheimer's disease. It is unknown how th e deposits are formed, but several studies have suggested that proteas es might play a crucial role. Consequently, the search for proteases r esponsible for processing tau and amyloid precursor protein has become relevant. Here, the ability of thrombin to process tau in vitro is ex amined. Thrombin, which is found in blood but presumably also in the n ervous system, cleaves tau and generates a stable 25 kDa fragment. Imm unoblot and amino acid sequencing reveals that the fragment is derived from the C-terminal of tau, and a microtubule assembly assay shows th at it has a reduced capacity to promote microtubule assembly compared with full length tau. (C) 1994 Academic Press, Inc.