Expression of apoptosis related proteins: RAIDD, ZIP kinase, Bim/BOD, p21, Bax, Bcl-2 and NF-kB in brains of patients with Down syndrome

  • E. Engidawork
  • T. Gulesserian
  • R. Seidl
  • N. Cairns
  • G. Lubec


Down syndrome (DS) is a genetic disease that exhibits significant neuropathological parallels with Alzheimer’s disease (AD). One of the features of DS, neuronal loss, has been hypothesized to occur as a result of apoptosis. An increasing number of proteins are implicated in apoptosis and several of them were shown to be altered in AD, however, the knowledge in DS is far from complete. To further substantiate the hypothesis that apoptosis is the underlying mechanism for neuronal loss and contribute towards the current knowledge of apoptosis in DS, we analyzed the expression of apoptosis related proteins in frontal cortex and cerebellum of DS by western blot and ELISA techniques. Quantitative analysis revealed a significant increase in DS frontal (P < 0.0001) and cerebellar (P < 0.05) Bim/BOD (Bcl-2 interacting mediator of cell death/Bcl-2 related ovarian death gene), cerebellar Bcl-2 (P < 0.01) as well as p21 (P < 0.05) levels compared to controls. No significant change was detected in Bax, RAIDD (receptor interacting protein (RIP)-associated ICH-l/CED-3-homologus protein with death domain), ZIP (Zipper interacting protein) kinase and NF-kB p65 levels in both regions, although frontal cortex levels of RAIDD, Bcl-2 and p21 levels tended to increase. In addition, a 45 kDa truncated form of NF-kB p65 displayed a significant elevation (P < 0.05) in DS cerebellum. No significant correlation had been obtained between postmortem interval and level of the proteins analyzed. With regard to age, it was only NF-kB p65 that showed significant correlation (r = -0.8964, P = 0.0155, n = 9) in frontal cortex of controls. These findings provide further evidence that apoptosis indeed accounts for the neuronal loss in DS but Bax and RAIDD do not appear to take part in this process.


Frontal Cortex Down Syndrome Postmortem Interval Apoptosis Related Protein Receptor Interact Protein 


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Copyright information

© Springer-Verlag/Wien 2001

Authors and Affiliations

  • E. Engidawork
    • 1
  • T. Gulesserian
    • 1
  • R. Seidl
    • 1
  • N. Cairns
    • 2
  • G. Lubec
    • 1
  1. 1.Department of PediatricsUniversity of ViennaAustria
  2. 2.Department of Neuropathology, Institute of PsychiatryKing’s CollegeLondonUK

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