title: Truncated tau from sporadic Alzheimer's disease suffices to drive neurofibrillary degeneration in vivo.
abstract: 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.
authors.affiliation: Axon Neuroscience GmbH, Rennweg 95b, 1030 Vienna, Austria.
authors.forename: Norbert
authors.initials: N
authors.lastname: Zilka
authors.forename: Peter
authors.initials: P
authors.lastname: Filipcik
authors.forename: Peter
authors.initials: P
authors.lastname: Koson
authors.forename: Lubica
authors.initials: L
authors.lastname: Fialova
authors.forename: Rostislav
authors.initials: R
authors.lastname: Skrabana
authors.forename: Monika
authors.initials: M
authors.lastname: Zilkova
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rolkova
authors.forename: Eva
authors.initials: E
authors.lastname: Kontsekova
authors.forename: Michal
authors.initials: M
authors.lastname: Novak
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011485:Protein Binding; D051381:Rats; D012995:Solubility; D013116:Spinal Cord / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016875:tau Proteins