Elsevier

Neuroscience

Volume 91, Issue 1, June 1999, Pages 1-5
Neuroscience

Letter to Neuroscience
Elevated expression of p21ras is an early event in Alzheimer's disease and precedes neurofibrillary degeneration

https://doi.org/10.1016/S0306-4522(99)00059-7Get rights and content

Abstract

Alzheimer's disease is a chronic degenerative disorder characterized by the intracellular accumulation of “paired helical filaments” consisting of highly phosphorylated tau and by extracellular deposits of aggregated Aβ-peptide. Furthermore, neurodegeneration in Alzheimer's disease is associated with the appearance of neuritic growth profiles that are aberrant with respect to their localization, morphological appearance, and composition of cytoskeletal elements.2 During early stages of Alzheimer's disease, a variety of growth factors and mitogenic compounds10., 12., 15., 16., 18., 32. are elevated. Most of these factors mediate their cellular effects through activation of the p21ras-dependent mitogen-activated protein kinase cascade, a pathway that is also involved in the regulation of expression and post-translational modification of the amyloid precursor protein and tau protein.7., 11., 13., 14., 19., 20., 22., 31. We previously reported on the elevated expression of p21ras associated with paired helical filament formation and Aβ-deposits.17 However, the question arises as to whether induction of p21ras and the downstream mitogen-activated protein kinase cascade is an early event with rather primary importance in the pathogenetic chain or simply occurs as a cellular response to neurodegeneration.29 The present study shows that expression of p21ras is clearly elevated in very early stages of the disease, preceding both neurofibrillary pathology and formation of Aβ.

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Acknowledgements

This study was supported by the Bundesministerium fur Bildung, Forschung und Technologie (BMBF), Interdisziplinäres Zentrum für Klinische Forschung (IZKF) at the University of Leipzig (O1KS9504, Project C1).

References (35)

  • Arendt Th., Holzer M., Gärtner U. and Brückner M. K. (1998) Aberrancies in signal transduction and cell cycle related...
  • Th. Arendt et al.

    Expression of the cyclin-dependent kinase inhibitor pl6 in Alzheimer's disease

    NeuroReport

    (1996)
  • H. Braak et al.

    Neuropathological staging of Alzheimer-related changes

    Acta neuropath., Berlin

    (1991)
  • J. Busser et al.

    Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer's disease brain

    J. Neurosci.

    (1998)
  • J.M. Cosgaya et al.

    Nerve growth factor and ras regulate beta-amyloid precursor protein gene expression in PC12 cells

    J. Neurochem.

    (1996)
  • K.A. Crutcher et al.

    Detection of NGF-like activity in human brain tissue: increased levels in Alzheimers disease

    J. Neurosci.

    (1993)
  • J. Desdouits-Magnen et al.

    Regulation of secretion of Alzheimer amyloid precursor protein by the mitogen-activated protein kinase cascade

    J. Neurochem.

    (1998)
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