Journal
FEBS LETTERS
Volume 580, Issue 15, Pages 3582-3588Publisher
WILEY
DOI: 10.1016/j.febslet.2006.05.029
Keywords
Alzheimer's disease; truncated tau; microtubule assembly; neurofibrillary degeneration; sarcosyl insoluble tau; tau cascade
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Truncated tau protein is the characteristic feature of human sporadic Alzheimer's disease. We have identified truncated tau proteins conformationally different from normal healthy tau. Subpopulations of these structurally different tau species promoted abnormal microtubule assembly in vitro suggesting toxic gain of function. To validate pathological activity in vivo we expressed active form of human truncated tau protein as transgene, in the rat brain. Its neuronal expression led to the development of the neurofibrillary degeneration of Alzheimer's type. Furthermore, biochemical analysis of neurofibrillary changes revealed that massive sarcosyl insoluble tau complexes consisted of human Alzheimer's tau and endogenous rat tau in ratio 1:1 including characteristic Alzheimer's disease (AD)-specific proteins (A68). This work represents first insight into the possible causative role of truncated tau in AD neurofibrillary degeneration in vivo. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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