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 Aβ 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".
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Author information
Authors and Affiliations
Additional information
Electronic Publication
Rights and permissions
About this article
Cite this article
Veerhuis, R., Van Breemen, M.J., Hoozemans, J.J. et al. Amyloid β plaque-associated proteins C1q and SAP enhance the Aβ1–42 peptide-induced cytokine secretion by adult human microglia in vitro. Acta Neuropathol 105, 135–144 (2003). https://doi.org/10.1007/s00401-002-0624-7
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s00401-002-0624-7