BACE-2 is overexpressed in Down's syndrome

L. Barbiero, L. Benussi, R. Ghidoni, A. Alberici, C. Russo, G. Schettini, S. F. Pagano, E. A. Parati, F. Mazzoli, F. Nicosia, S. Signorini, E. Feudatari, G. Binetti

Research output: Contribution to journalArticle

Abstract

Brain deposition of the amyloid-β protein (Aβ) is a frequent complication of Down's syndrome (DS) patients. Aβ peptide is generated by endoproteolytic processing of Aβ precursor protein by γ and β secretases. Recently a transmembrane aspartyl protease, BACE, has been identified as the β-secretase, and its homologous BACE-2 has also been described. BACE-2 gene resides on chromosome 21 in the obligate DS region. It cleaves Aβ precursor protein at its β site and more efficiently at a different site within Aβ. In the present study we characterized the BACE-2 gene and protein expression in the DS patients and healthy control. We analyzed, by using a nonradioactive ribonuclease protection assay, the levels of BACE-2 mRNA expression in primary skin fibroblasts. The analysis revealed a 2.6-fold increase in BACE-2 mRNA levels in the DS group compared to the levels observed in the control group. Western blot analysis revealed no difference between DS and control in BACE-2 protein levels in the intracellular compartment. In the medium conditioned by fibroblast, we revealed an evident secretion of BACE-2 protein, represented by two different molecular weights, remarkably increased in DS fibroblasts. BACE-2 overexpression was also confirmed in the DS fetal brains and human neural embryonic DS stem cells in which conditioned media BACE-2 was secreted. These data highlight the importance of the extracellular compartment where BACE-2 overexpression could play a role in plaque formation in DS patients.

Original languageEnglish
Pages (from-to)335-345
Number of pages11
JournalExperimental Neurology
Volume182
Issue number2
DOIs
Publication statusPublished - Aug 1 2003

Keywords

  • β-Secretase
  • Alzheimer disease
  • Amyloid precursor protein
  • APP processing
  • BACE-2
  • Down's syndrome
  • Embryonic neural stem cells
  • Fetal brain
  • Fibroblasts
  • Overexpression

ASJC Scopus subject areas

  • Neuroscience(all)
  • Neurology

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  • Cite this

    Barbiero, L., Benussi, L., Ghidoni, R., Alberici, A., Russo, C., Schettini, G., Pagano, S. F., Parati, E. A., Mazzoli, F., Nicosia, F., Signorini, S., Feudatari, E., & Binetti, G. (2003). BACE-2 is overexpressed in Down's syndrome. Experimental Neurology, 182(2), 335-345. https://doi.org/10.1016/S0014-4886(03)00049-9