Alzheimer’s pathogenesis: is there neuron-to-neuron propagation? View Full Text


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Article Info

DATE

2011-04-24

AUTHORS

Heiko Braak, Kelly Del Tredici

ABSTRACT

There is increasing interest in the early phase of Alzheimer’s disease before severe neuronal dysfunction occurs, but it is still not known when or where in the central nervous system the underlying pathological process begins. In this review, we discuss the idea of possible disease progression from the locus coeruleus to the transentorhinal region of the cerebral cortex via neuron-to-neuron transmission and transsynaptic transport of tau protein aggregates, and we speculate that such a mechanism together with the very long prodromal period that characterizes Alzheimer’s disease may be indicative of a prion-like pathogenesis for this tauopathy. The fact that AT8-immunoreactive abnormal tau aggregates (pretangles) develop within proximal axons of noradrenergic coeruleus projection neurons in the absence of both tau lesions (pretangles, NFTs/NTs) in the transentorhinal region as well as cortical amyloid-β pathology means that currently used neuropathological stages for Alzheimer’s disease will have to be reclassified. More... »

PAGES

589-595

References to SciGraph publications

  • 2010-04. Prion-like transmission of protein aggregates in neurodegenerative diseases in NATURE REVIEWS MOLECULAR CELL BIOLOGY
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  • 2009-11-19. Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update in ACTA NEUROPATHOLOGICA
  • 2010-05-02. Why Pleiotropic Interventions are Needed for Alzheimer's Disease in MOLECULAR NEUROBIOLOGY
  • 2007-09. Tau-mediated neurodegeneration in Alzheimer's disease and related disorders in NATURE REVIEWS NEUROSCIENCE
  • 2009-02-04. The locus coeruleus and noradrenergic modulation of cognition in NATURE REVIEWS NEUROSCIENCE
  • 2007-03-20. Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau in ACTA NEUROPATHOLOGICA
  • 1994-06. A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads in ACTA NEUROPATHOLOGICA
  • 2006. Molecular and cellular pathways towards and away from Alzheimer’s disease in ALZHEIMER: 100 YEARS AND BEYOND
  • 2009-01-30. Mechanisms of tau-induced neurodegeneration in ACTA NEUROPATHOLOGICA
  • 2008-04-23. Membrane nanotubes: dynamic long-distance connections between animal cells in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2010-07-09. Soluble hyper-phosphorylated tau causes microtubule breakdown and functionally compromises normal tau in vivo in ACTA NEUROPATHOLOGICA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00401-011-0825-z

    DOI

    http://dx.doi.org/10.1007/s00401-011-0825-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1033550772

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21516512


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