Amyloid β plaque-associated proteins C1q and SAP enhance the Aβ1-42 peptide-induced cytokine secretion by adult human microglia in vitro

Robert Veerhuis, Mariëlle J. Van Breemen, Jeroen J M Hoozemans, Michela Morbin, Jamal Ouladhadj, Fabrizio Tagliavini, Piet Eikelenboom

Research output: Contribution to journalArticle

Abstract

Pro-inflammatory cytokines released by activated microglia could be a driving force in Alzheimer's disease (AD) pathology. We evaluated whether the presence of complement factor C1q and serum amyloid P component (SAP) in Aβ deposits is related to microglial activation. Activated microglia accumulate in SAP-and C1q-immunoreactive fibrillar amyloid β (Aβ) plaques in AD temporal cortex. No clustered microglia are seen in SAP-and C1q-positive circumscript, non-fibrillar, tau-negative Aβ plaques in AD caudate nucleus and non-demented control temporal cortex. In addition, no clustered microglia were observed in C1q-and SAP-negative, irregular shaped, diffuse plaques in AD caudate nucleus and in non-demented control temporal cortex, which suggests that microglia are attracted and activated in AD deposits of certain fibrillarity that, in addition, have fixed SAP and C1q. Therefore, the effects of Aβ1-42, SAP and C1q on cytokine secretion by human postmortem microglia in vitro were assessed. Aβ1-42 alone had little to no effect. Aβ1-42 peptides in combination with C1q or C1q and SAP increased microglial interleukin (IL)-6 secretion four-and eightfold, respectively. Tumor necrosis factor (TNF)-α, as well as intracellular IL- 1α and IL-1β levels, also increased upon exposure of microglia to Aβ1-42-SAP-C1q complexes. Combined with earlier findings, that amyloid and activated microglia accumulate at a relatively early stage of cognitive decline in AD patients, this suggests that clustering of activated, cytokine-secreting microglia in SAP-and C1q-containing Aβ deposits precedes neurodegenerative changes in AD, and thus may provide a "therapeutic window".

Original languageEnglish
Pages (from-to)135-144
Number of pages10
JournalActa Neuropathologica
Volume105
Issue number2
Publication statusPublished - Feb 1 2003

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • C1q
  • Microglia
  • Serum amyloid P

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

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  • Cite this

    Veerhuis, R., Van Breemen, M. J., Hoozemans, J. J. M., Morbin, M., Ouladhadj, J., Tagliavini, F., & Eikelenboom, P. (2003). Amyloid β plaque-associated proteins C1q and SAP enhance the Aβ1-42 peptide-induced cytokine secretion by adult human microglia in vitro. Acta Neuropathologica, 105(2), 135-144.