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

  • S. M. de la Monte
Conference paper


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.


Down Syndrome Dystrophic Neurites Ts65DN Mouse Down Syndrome Brain Down Syndrome Cell Adhesion Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Down Syndrome


Alzheimer’s disease


superoxide dismutase I


amyloid precursor protein


growth-associated protein-43


neuronal thread protein


nitric oxide synthase


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Copyright information

© Springer-Verlag Wien 1999

Authors and Affiliations

  • S. M. de la Monte
    • 1
    • 2
  1. 1.Harvard Medical SchoolPathology and Neuropathology, and Massachusetts General HospitalBostonUSA
  2. 2.Departments of Medicine and Pathology, Rhode Island HospitalBrown University School of MedicineProvidenceUSA

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