An impairment of the microglial catabolic mechanisms allows amyloid- (A) 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 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 A42-stimulated cell cultures showed that significantly higher percentages of inflammatoryM/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/A42 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 peptides in an MHC-restricted fashion. Therapeutic approaches designed to interrupt these mechanism might prove beneficial.
A Complex Proinflammatory Role for Peripheral Monocytes in Alzheimer's Disease / M. Saresella, I. Marventano, E. Calabrese, F. Piancone, V. Rainone, A. Gatti, M. Alberoni, R. Nemni, M. Clerici. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - 38:2(2014), pp. 403-413.
|Titolo:||A Complex Proinflammatory Role for Peripheral Monocytes in Alzheimer's Disease|
CLERICI, MARIO SALVATORE (Ultimo)
|Parole Chiave:||Alzheimer’s disease; cytokines; monocytes; neuroinflammation; toll-like receptors|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
Settore MED/04 - Patologia Generale
|Data di pubblicazione:||2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3233/JAD-131160|
|Appare nelle tipologie:||01 - Articolo su periodico|