title: A deficiency in CCR2+ monocytes: the hidden side of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by intracellular neurofibrillary tangle formation and extracellular amyloid-β (Aβ) deposition. To date, microglia seem to act as double-edged swords, being either beneficial (e.g. clearance of Aβ) or detrimental (e.g. secretion of neurotoxic factors) in AD. Following a rather intense debate on the question, a consensus has emerged that microglia can renew themselves via proliferation of already differentiated microglia as well as via the de novo recruitment of monocytes of mouse models of AD. However, recent advances suggest distinct function for resident and bone marrow-derived microglia (BMDM), and have emphasized the neuroprotective functions of BMDM. BMDM is the only subset of cells that restrict cerebral amyloidosis in the AD brain, which has been recently attributed to CCR2(+) monocytes. Moreover, an impaired recruitment of CCR2(+) monocytes has been reported in AD patients, as seen from the CCR2(+) monocytopenia found in the bloodstream and BM. The present review summarizes the current knowledge on the roles and dysfunctions of CCR2(+) monocytes in AD and their potential as key therapeutic targets.
authors.affiliation: Neuroscience Laboratory, CHU de Québec Research Center and Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier Boulevard, Québec, QC, Canada G1V 4G2.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Naert
authors.forename: Serge
authors.initials: S
authors.lastname: Rivest
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism; D006801:Humans; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D054390:Receptors, CCR2 / Q000172:deficiency* / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D054390:Receptors, CCR2
keywords: Alzheimer's disease; CCR2; CX3CR1; M-CSF; bone marrow-derived microglia; cytokines; monocytes