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Brain hypometabolism triggers PHF-like phosphorylation of tau, a major hallmark of Alzheimer’s disease pathology

  • Neurology and Preclinical Neurological Studies - Review Article
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Abstract

Sporadic Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disorder of unknown cause characterized by fibrillar accumulation of the Aß-peptide and aggregates of the microtubule-associated protein tau in a hyperphosphorylated form. Already at preclinical stages, AD is characterized by hypometabolic states which are a good predictor of cognitive decline. Here, we summarize recent evidence derived from the study of hibernating animals that brain hypometabolism can trigger PHF-like hyperphosphorylation of tau. We put forward the concept that particular types of neurons respond to a hypometabolic state with an elevated phosphorylation of tau protein which represents a physiological mechanism involved in regulating synaptic gain. If, in contrast to hibernation, the hypometabolic state is not terminated after a definite time but rather persists and progresses, the elevated phosphorylation of tau protein endures and the protective reaction associated with it might turn into a pathological cascade leading to neurodegeneration.

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Authors and Affiliations

  1. Paul Flechsig Institute of Brain Research, University of Leipzig, Jahnallee 59, 04109, Leipzig, Germany

    Thomas Arendt, Jens Stieler & Max Holzer

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  1. Thomas Arendt
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  2. Jens Stieler
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  3. Max Holzer
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Correspondence to Thomas Arendt.

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This paper is dedicated to the memory of Siegfried Hoyer who pioneered the pathogenetic concept of energy hypometabolism in Alzheimer’s disease.

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Arendt, T., Stieler, J. & Holzer, M. Brain hypometabolism triggers PHF-like phosphorylation of tau, a major hallmark of Alzheimer’s disease pathology. J Neural Transm 122, 531–539 (2015). https://doi.org/10.1007/s00702-014-1342-8

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  • DOI: https://doi.org/10.1007/s00702-014-1342-8

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