Aβ and tau prions feature in the neuropathogenesis of Down syndrome

  • Carlo Condello
    Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, CA 94158
  • Alison M. Maxwell
    Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158
  • Erika Castillo
    Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, CA 94158
  • Atsushi Aoyagi
    Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, CA 94158
  • Caroline Graff
    Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Solna, Sweden 171 77
  • Martin Ingelsson
    Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden SE-751 05
  • Lars Lannfelt
    Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden SE-751 05
  • Thomas D. Bird
    Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA 98195
  • C. Dirk Keene
    Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA 98115
  • William W. Seeley
    Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA 94158
  • Daniel P. Perl
    Department of Pathology (Neuropathology), F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814
  • Elizabeth Head
    Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697
  • Stanley B. Prusiner
    Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, CA 94158

抄録

<jats:p>Down syndrome (DS) is caused by the triplication of chromosome 21 and is the most common chromosomal disorder in humans. Those individuals with DS who live beyond age 40 y develop a progressive dementia that is similar to Alzheimer’s disease (AD). Both DS and AD brains exhibit numerous extracellular amyloid plaques composed of Aβ and intracellular neurofibrillary tangles composed of tau. Since AD is a double-prion disorder, we asked if both Aβ and tau prions feature in DS. Frozen brains from people with DS, familial AD (fAD), sporadic AD (sAD), and age-matched controls were procured from brain biorepositories. We selectively precipitated Aβ and tau prions from DS brain homogenates and measured the number of prions using cellular bioassays. In brain extracts from 28 deceased donors with DS, ranging in age from 19 to 65 y, we found nearly all DS brains had readily measurable levels of Aβ and tau prions. In a cross-sectional analysis of DS donor age at death, we found that the levels of Aβ and tau prions increased with age. In contrast to DS brains, the levels of Aβ and tau prions in the brains of 37 fAD and sAD donors decreased as a function of age at death. Whether DS is an ideal model for assessing the efficacy of putative AD therapeutics remains to be determined.</jats:p>

収録刊行物

被引用文献 (1)*注記

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ