A Complex Proinflammatory Role for Peripheral Monocytes in Alzheimer's Disease

作者：Saresella Marina^*; Marventano Ivana; Calabrese Elena; Piancone Federica; Rainone Veronica; Gatti Andrea; Alberoni Margherita; Nemni Raffaello; Clerici Mario

来源：Journal of Alzheimer's Disease, 2014, 38(2): 403-413.

DOI：10.3233/JAD-131160

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

An impairment of the microglial catabolic mechanisms allows amyloid-beta (A beta) 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 A beta 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 A beta(42)-stimulated cell cultures showed that significantly higher percentages of inflammatoryM/M(CD14(+) CD16(-)CCR2(++) CX3CR1(low)) 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/A beta(42) 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 A beta peptides in an MHC-restricted fashion. Therapeutic approaches designed to interrupt these mechanism might prove beneficial.

• 出版日期2014