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Molecular abnormalities of the brain in Down Syndrome: relevance to Alzheimer’s neurodegeneration

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The Molecular Biology of Down Syndrome

Summary

Down syndrome is caused by over-expression of genes located within a segment of chromosome 21, termed the Down locus. Down syndrome is associated with developmental abnormalities of the central nervous system that result in mental retardation and age-dependent Alzheimer-type neurodegeneration. Some of the neurodegenerative lesions, including Aβ amyloid eposition, apoptotic cell death, and aberrant dendritic arborization, are in part due to constitutively increased expression of genes that encode the amyloid precursor protein, superoxide dismutase I, and S100-beta, and located within the Down locus. However, neurodegeneration in Down syndrome is also associated with aberrant expression of genes that are not linked to the Down locus, including the growth associated protein, GAP-43, nitric oxide synthase 3, neuronal thread protein, and pro-apoptosis genes such as p53, Bax, and interleukin-1β-converting enzyme. Increased expression of these non-Down locus genes correlates with proliferation of dystrophic neuntes and apoptotic cell death, two important correlates of cognitive impairment in Alzheimer’s disease. This article reviews the functional importance of abnormal gene expression in relation to Alzheimer-type neurodegeneration in brains of individuals with Down syndrome.

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Abbreviations

DS:

Down Syndrome

AD:

Alzheimer’s disease

SODI:

superoxide dismutase I

APP:

amyloid precursor protein

GAP-43:

growth-associated protein-43

NTP:

neuronal thread protein

NOS:

nitric oxide synthase

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Author information

Authors and Affiliations

  1. Harvard Medical School, Pathology and Neuropathology, and Massachusetts General Hospital, Boston, MA, USA

    Dr. S. M. de la Monte

  2. Departments of Medicine and Pathology, Rhode Island Hospital, Brown University School of Medicine, 55 Claverick Street, Room 419, Providence, RI, 02403, USA

    Dr. S. M. de la Monte

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  1. Dr. S. M. de la Monte
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Editors and Affiliations

  1. Universitäts-Kinderklinik, Wien, Österreich

    G. Lubec

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© 1999 Springer-Verlag Wien

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de la Monte, S.M. (1999). Molecular abnormalities of the brain in Down Syndrome: relevance to Alzheimer’s neurodegeneration. In: Lubec, G. (eds) The Molecular Biology of Down Syndrome. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6380-1_1

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  • DOI: https://doi.org/10.1007/978-3-7091-6380-1_1

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83377-3

  • Online ISBN: 978-3-7091-6380-1

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