title: A complex proinflammatory role for peripheral monocytes in Alzheimer's disease.
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.
authors: Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi ONLUS Foundation IRCCS, Milano, Italy.
authors: Marina
authors: M
authors: Saresella
authors: Ivana
authors: I
authors: Marventano
authors: Elena
authors: E
authors: Calabrese
authors: Federica
authors: F
authors: Piancone
authors: Veronica
authors: V
authors: Rainone
authors: Andrea
authors: A
authors: Gatti
authors: Margherita
authors: M
authors: Alberoni
authors: Raffaello
authors: R
authors: Nemni
authors: Mario
authors: M
authors: Clerici
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D002478:Cells, Cultured; D060825:Cognitive Dysfunction / Q000276:immunology / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D010446:Peptide Fragments; D051193:Toll-Like Receptors; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; cytokines; monocytes; neuroinflammation; toll-like receptors