Down's Syndrome: Up-Regulation of β-Amyloid Protein Precursor and τ mRNAs and Their Defective Coordination

Authors

  • Fumitaka Oyama,

    1. Division of Biomedical Polymer Science, Institute for Comprehensive Medical Science, School of Medicine, Fujita Health University, Aichi
    2. Department of Neuropathology, Institute for Brain Research, Faculty of Medicine, University of Tokyo
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  • Nigel J. Cairns,

    1. Department of Pathology, Tokyo Medical College, Tokyo, Japan
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  • Hiroyuki Shimada,

    1. MRC Alzheimer's Disease Brain Bank, Department of Neuropathology, Institute of Psychiatry, London, England
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  • Rieko Oyama,

    1. Division of Biomedical Polymer Science, Institute for Comprehensive Medical Science, School of Medicine, Fujita Health University, Aichi
    2. Department of Neuropathology, Institute for Brain Research, Faculty of Medicine, University of Tokyo
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  • Koiti Titani,

    1. Division of Biomedical Polymer Science, Institute for Comprehensive Medical Science, School of Medicine, Fujita Health University, Aichi
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  • Yasuo Ihara

    Corresponding author
    1. Department of Neuropathology, Institute for Brain Research, Faculty of Medicine, University of Tokyo
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Address correspondence and reprint requests to Dr. Y. Ihara at Department of Neuropathology, Institute for Brain Research, Faculty of Medicine, University of Tokyo, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113, Japan.

Abstract

Abstract: Almost all patients >40 years of age with Down's syndrome (DS) develop the pathology characteristic of Alzheimer's disease: abundant β-amyloid plaques and neurofibrillary tangles. We have investigated the gene expression of β-amyloid protein precursor (APR) and τ in DS and age-matched control brains and found that levels of both mRNAs were significantly elevated in DS. Such up-regulation was not observed in two other neuronal proteins. A correlation between total APP and τ mRNA levels was also found in DS brain but distinct from the pattern observed in normal brain. Although a proportionality existed between APP-695 mRNA and three-repeat τ mRNA in DS, the proportionality between APP-751 mRNA and four-repeat τ mRNA, which is normally present, was not observed. Thus, DS brains are primarily characterized by the up-regulation of τ mRNA as well as APP mRNA and disruption of the coordinate expression between APP-751 and four-repeat τ.

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