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Hibernation model of tau phosphorylation in hamsters: selective vulnerability of cholinergic basal forebrain neurons – implications for Alzheimer's disease

Authors

  • Wolfgang Härtig,

    1. Departments of Neurochemistry and Neuroanatomy, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany
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  • Jens Stieler,

    1. Departments of Neurochemistry and Neuroanatomy, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany
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  • Ate S. Boerema,

    1. Department of Chronobiology, University of Groningen, Kerklaan 30, 9751 NN Haren, the Netherlands
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  • Jennifer Wolf,

    1. Departments of Neurochemistry and Neuroanatomy, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany
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  • Udo Schmidt,

    1. Departments of Neurochemistry and Neuroanatomy, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany
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  • Jana Weißfuß,

    1. Departments of Neurochemistry and Neuroanatomy, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany
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  • Torsten Bullmann,

    1. Departments of Neurochemistry and Neuroanatomy, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany
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  • Arjen M. Strijkstra,

    1. Department of Chronobiology, University of Groningen, Kerklaan 30, 9751 NN Haren, the Netherlands
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  • Thomas Arendt

    1. Departments of Neurochemistry and Neuroanatomy, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany
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Dr W. Härtig, as above.
E-mail: hartig@medizin.uni-leipzig.de

Abstract

Neurofibrillar tangles made up of ‘paired helical filaments’ (PHFs) consisting of hyperphosphorylated microtubule-associated protein tau are major hallmarks of Alzheimer's disease (AD). Tangle formation selectively affects certain neuronal types and systematically progresses throughout numerous brain areas, which reflects a hierarchy of neuronal vulnerability and provides the basis for the neuropathological staging of disease severity. Mechanisms underlying this selective neuronal vulnerability are unknown. We showed previously that reversible PHF-like phosphorylation of tau occurs during obligate hibernation. Here we extend these findings to facultative hibernators such as Syrian hamsters (Mesocricetus auratus) forced into hibernation. In this model, we showed in the basal forebrain projection system that cholinergic neurons are selectively affected by PHF-like phosphorylated tau, while γ-aminobutyric acid (GABA)ergic neurons are largely spared, which shows strong parallels to the situation in AD. Formation of PHF-tau in these neurons apparently does not affect their function as pacemaker for terminating hibernation. We conclude that although formation of PHF-like phosphorylated tau in the mammalian brain follows a certain hierarchy, affecting some neurons more frequently than others, it is not necessarily associated with impaired neuronal function and viability. This indicates a more general link between PHF-like phosphorylation of tau and the adaptation of neurons under conditions of a ‘vita minima’.

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