title: Brain hypometabolism triggers PHF-like phosphorylation of tau, a major hallmark of Alzheimer's disease pathology.
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.
authors.affiliation: Paul Flechsig Institute of Brain Research, University of Leipzig, Jahnallee 59, 04109, Leipzig, Germany, aret@medizin.uni-leipzig.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Arendt
authors.forename: Jens
authors.initials: J
authors.lastname: Stieler
authors.forename: Max
authors.initials: M
authors.lastname: Holzer
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006605:Hibernation / Q000502:physiology; D006801:Humans; D016202:N-Methylaspartate / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D016202:N-Methylaspartate