A complex proinflammatory role for peripheral monocytes in Alzheimer's disease

Marina Saresella, Ivana Marventano, Elena Calabrese, Federica Piancone, Veronica Rainone, Andrea Gatti, Margherita Alberoni, Raffaello Nemni, Mario Clerici

Research output: Contribution to journalArticlepeer-review

Abstract

An impairment of the microglial catabolic mechanisms allows amyloid-β (Aβ) accumulation in plaques within the brain in Alzheimer's disease (AD). Monocytes/macrophages (M/M) are activated in AD and migrate thorough the blood-brain barrier (BBB) trying to improve Aβ clearing. In the attempt to shed light on the role of M/M in AD, these cells were analyzed in patients with AD or mild cognitive impairment (MCI) and in age-matched healthy controls. Results obtained in Aβ42-stimulated cell cultures showed that significantly higher percentages of inflammatory M/M (CD14+ CD16 -CCR2++CX3CR1low) expressing toll like receptors (TLR) 2 and 4, as well as IL-6 and CCR2, a chemokine favoring M/M migration through the BBB, are seen in AD. Confocal microscopy suggested the presence of MHC-II/Aβ42 complexes on AD M/M alone. Finally, TRL3-and TLR8-expressing and IL-23-producing M/M were increased in both AD and MCI compared to HC. These data indicate that M/M in AD are characterized by an inflammatory profile and are involved in the induction of both innate immune responses via TLR stimulation and of acquired immunity possibly secondarily to the presentation of Aβ peptides in an MHC-restricted fashion. Therapeutic approaches designed to interrupt these mechanism might prove beneficial.

Original languageEnglish
Pages (from-to)403-413
Number of pages11
JournalJournal of Alzheimer's Disease
Volume38
Issue number2
DOIs
Publication statusPublished - 2014

Keywords

  • Alzheimer's disease
  • cytokines
  • monocytes
  • neuroinflammation
  • toll-like receptors

ASJC Scopus subject areas

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

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