Immunoproteasome and LMP2 polymorphism in aged and Alzheimer's disease brains

Michele Mishto, Elena Bellavista, Aurelia Santoro, Alexandra Stolzing, Claudia Ligorio, Benedetta Nacmias, Liana Spazzafumo, Martina Chiappelli, Federico Licastro, Sandro Sorbi, Annalisa Pession, Thomas Ohm, Tilman Grune, Claudio Franceschi

Research output: Contribution to journalArticle

Abstract

In this study, we investigated the presence and role of immunoproteasome and its LMP2 subunit polymorphism at codon 60 in Alzheimer's disease (AD). Immunoproteasome was present in brain areas such as hippocampus and cerebellum and localized in neurons, astrocytes and endothelial cells. A higher expression of immunoproteasome was found in brain of AD patients than in brain of non-demented elderly, being its expression in young brain negligible or absent. Furthermore, AD affected regions showed a partial decrease in proteasome trypsin-like activity. The study of LMP2 polymorphism (R/H) showed that it does not influence LMP2 expression (neither the mRNA nor mature protein) in brain tissue. However, control brain areas of AD patients carrying the RR genotype showed an increased proteasome activity in comparison with RH carriers. To test whether this effect of the genotype might be related to AD onset we performed a genetic study, which allowed us to exclude an association of LMP2 codon 60 polymorphism with AD onset, despite its influence on the proteasome activity in human brain.

Original languageEnglish
Pages (from-to)54-66
Number of pages13
JournalNeurobiology of Aging
Volume27
Issue number1
DOIs
Publication statusPublished - Jan 2006

Keywords

  • Ageing
  • Alzheimer's disease
  • Immunoproteasome
  • LMP2 polymorphism
  • Neuroinflammation
  • Proteasome

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)

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  • Cite this

    Mishto, M., Bellavista, E., Santoro, A., Stolzing, A., Ligorio, C., Nacmias, B., Spazzafumo, L., Chiappelli, M., Licastro, F., Sorbi, S., Pession, A., Ohm, T., Grune, T., & Franceschi, C. (2006). Immunoproteasome and LMP2 polymorphism in aged and Alzheimer's disease brains. Neurobiology of Aging, 27(1), 54-66. https://doi.org/10.1016/j.neurobiolaging.2004.12.004