Down syndrome patients start early prenatal life with normal cholinergic, monoaminergic and serotoninergic innervation

  • B. Lubec
  • B. C. Yoo
  • M. Dierssen
  • N. Balic
  • G. Lubec


Apoptosis has been implicated in the selective neuronal loss of Down syndrome (DS). Apoptosis activates a family of cysteine proteases with specificity for aspartic acid residues referred to as caspases that play a key role in dismantling a cell committed to die. Caspase activity is regulated by a variety of proteins that possess a domain resembling the prodomains of caspases. Little is known, however, about the changes of caspases and their regulatory proteins in DS. Here, we investigated levels of nine such different proteins by western blot technique in frontal cortex and cerebellum of control and DS subjects. The protein levels of DFF45 (DNA fragmentation factor 45), and FLIP (FADD like interleukin-lß-converting enzyme inhibitory proteins) were significantly decreased whereas that of RICK (RIP-like interacting CLARP kinase) increased in both regions of DS. In contrast, cytochrome c, Apaf-1 (apoptosis protease activating factor-1), procaspase-9 and ARC (apoptosis repressor with caspase recruitment domain) were unchanged. Procaspase-3 and -8 were significantly decreased in frontal cortex but no significant change was observed in cerebellum. Regression analysis revealed no correlation between postmortem interval and levels of the investigated proteins. However, inconsistent correlation was found between age and levels of proteins as well as amongst the density of individual proteins. These findings demonstrate that dysregulation of apoptotic proteins does exist in DS brain and may underlie the neuropathology of DS. The study further suggests that apoptosis in DS may occur via the death receptor pathway independent of cytochrome c. Hence, therapeutic strategies that target caspase activation may prove useful in combating neuronal loss in this disorder.


Tyrosine Hydroxylase Down Syndrome Neuronal Density Cholinergic Innervation Down Syndrome Patient 
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Copyright information

© Springer-Verlag/Wien 2001

Authors and Affiliations

  • B. Lubec
    • 1
  • B. C. Yoo
    • 2
  • M. Dierssen
    • 3
  • N. Balic
    • 4
  • G. Lubec
    • 2
  1. 1.Department of NeonatologyUniversity of ViennaViennaAustria
  2. 2.Department of PediatricsUniversity of ViennaViennaAustria
  3. 3.Medical and Molecular Genetics Center-IROHospital Duran i ReynalsBarcelonaSpain
  4. 4.Institute of Medical and Chemical Laboratory DiagnosticsUniversity of ViennaViennaAustria

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