Down’s Syndrome and S-100 Protein

  • Robert Balázs
  • Ole S. Jørgensen
Part of the Altschul Symposia Series book series (ALSS, volume 2)


Down’s syndrome (DS) is a major known cause of mental retardation, accounting for 1 in about 1000 live births. This disorder is associated with aneuploidy affecting chromosome 21 and the characteristic features of the phenotype include premature aging, mental retardation, and Alzheimer type of neuropathology beyond the age of 35–40 (for reviews Epstein, 1986; Balázs and Brooksbank, 1985). DS is associated with duplication of all, or part of chromosome 21, resulting from meiotic non-disjunction or from translocation of part of the 21st chromosome to another chromosome. Analysis of DS patients with partial trisomy 21 suggests that the region critical for the DS phenotype includes the distal part of the long arm of chromosome 21 (the 21 q 22,2–22,3 region, e.g. McCormick et al., 1989). This segment contains only about 0.1% of the total genome and may comprise 50–100 genes (Patterson, 1987). In agreement with this, the screening of proteins and the in vitro translation products of the mRNAs of DS tissues revealed only limited changes, compared with controls (e.g. Whatley et al., 1984). It is generally believed that the abnormalities in DS result from an excess of a limited number of normal, rather than of the expression of abnormal gene products. For some of the trisomic genes in the DS critical region of chromosome 21, a gene dosage effect has been ascertained (gene products are present in 1.5 times normal, e.g. the cytoplasmic Cu+/Zn2+- superoxide dismutase, SOD, in the brain, Balázs and Brooksbank, 1985). However, the functional consequences of the gene dosage effect may be occasionally amplified (e.g. the antiviral response mediated through the interferon receptor mapped to chromosome 21; Epstein, 1986), while indirect effects by gene products coded on other chromosomes are also possible, the expression of which may be influenced by the imbalance in the genome. In spite of these qualifications DS may offer the possibility of approaching the question of how an extra set of normal genes can influence brain development. Further, any advancement in the elucidation of mechanisms involved in DS neuropathology may also facilitate a better understanding of the neurobiological mechanisms in Alzheimer’s disease (AD).


Glial Fibrillary Acidic Protein Down Syndrome Paired Helical Filament Neuronal Cell Adhesion Molecule Glial Fibrillary Acidic Protein Gene 
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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Robert Balázs
    • 1
  • Ole S. Jørgensen
    • 2
  1. 1.Netherlands Institute for Brain ResearchAmsterdamThe Netherlands
  2. 2.Institute of NeuropsychiatryUniversity of Copenhagen and Rigshospitalet-6102CopenhagenDenmark

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