title: Clogging of axons by tau, inhibition of axonal traffic and starvation of synapses.
abstract: Loss of synapses and dying back of axons are considered early events in brain degeneration during Alzheimer's disease. This is accompanied by an aberrant behavior of the microtubule-associated protein tau (hyperphosphorylation, aggregation). Since microtubules are the tracks for axonal transport, we are testing the hypothesis that tau plays a role in the malfunctioning of transport. Experiments with various neuronal and non-neuronal cells show that tau is capable of reducing net anterograde transport of vesicles and cell organelles by blocking the microtubule tracks. Thus, a misregulation of tau could cause the starvation of synapses and enhanced oxidative stress, long before tau detaches from microtubules and aggregates into Alzheimer neurofibrillary tangles. In particular, the transport of amyloid precursor protein is retarded when tau is elevated, suggesting a possible link between the two key proteins that show abnormal behavior in Alzheimer's disease.
authors.affiliation: Max-Planck-Unit for Structural Molecular Biology, Notkestrasse 85, 22607, Hamburg, Germany. mand@mpasmb.desy.de
authors.forename: E-M
authors.initials: EM
authors.lastname: Mandelkow
authors.forename: K
authors.initials: K
authors.lastname: Stamer
authors.forename: R
authors.initials: R
authors.lastname: Vogel
authors.forename: E
authors.initials: E
authors.lastname: Thies
authors.forename: E
authors.initials: E
authors.lastname: Mandelkow
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D051379:Mice; D008870:Microtubules / Q000378:metabolism / Q000473:pathology; D008959:Models, Neurological; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D015388:Organelles / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D022161:Transport Vesicles / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins