Increased pro-inflammatory response by dendritic cells from patients with Alzheimer's disease

Antonio Ciaramella, Federica Bizzoni, Francesca Salani, Diego Vanni, Gianfranco Spalletta, Nunzia Sanarico, Silvia Vendetti, Carlo Caltagirone, Paola Bossù

Research output: Contribution to journalArticle

Abstract

Alzheimer's disease (AD) is characterized by abnormal accumulation of amyloid-β peptide (Aβ) into extracellular fibrillar deposits, paralleled by chronic neuroinflammatory processes. Although Aβ seems to be causative in AD brain damage, the role of the immune system and its mechanisms still remain to be clarified. We have recently shown that normal monocyte-derived dendritic cells (MDDCs), when differentiated in the presence of Aβ -{1-42}, acquire an inflammatory phenotype and a reduced antigen presenting ability. Here we studied MDDCs derived from AD patients in comparison with MDDCs obtained from healthy control subjects (HC). MDDCs from AD patients, at variance with HC-derived cells, were characterized by an augmented cell recovery, a consistent increase in the expression of the pro-inflammatory ICAM-1 molecule, a decrease in the expression of the co-stimulatory CD40 molecule, and an impaired ability to induce T cell proliferation. Furthermore, MDDCs from AD produced higher amounts of IL-6 than HC-derived cells, confirming the more pronounced pro-inflammatory features of these cells in AD patients. Consistent results have been also obtained with monocytes, the MDDC precursors. In fact, while unstimulated monocytes do not appear to be different in AD and HC, after stimulation with lipopolysaccharide, AD monocytes overexpressed ICAM-1 with respect to controls, suggesting that common pathways of monocyte activation and MDDC differentiation are altered in AD. Overall, these findings show that AD-linked dysregulated immune mechanisms exist, which lead to dendritic cell-mediated over-activation of inflammation and impaired antigen presentation, thus supporting the view that immune cell activation could play an important role in AD pathogenesis.

Original languageEnglish
Pages (from-to)559-572
Number of pages14
JournalJournal of Alzheimer's Disease
Volume19
Issue number2
DOIs
Publication statusPublished - 2010

Keywords

  • Alzheimer's disease
  • Inflammation
  • Innate immune cells
  • Monocyte-derived dendritic cells
  • Monocytes

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

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