Distinct inflammatory phenotypes of microglia and monocyte‐derived macrophages in Alzheimer's disease models: effects of aging and amyloid pathology

• Published in: Aging cell Vol. 16; no. 1; pp. 27 - 38
• Main Authors: Martin, Elodie, Boucher, Céline, Fontaine, Bertrand, Delarasse, Cécile
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.02.2017; Wiley Open Access; John Wiley and Sons Inc
• Subjects: Advertising executives; Aging; Aging - pathology; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animals; CD36 Antigens - metabolism; Cell death; chemokines; Chemokines - metabolism; Comparative analysis; cytokines; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - pathology; Genetic aspects; Genetic engineering; Inflammation - pathology; Life Sciences; Lipopolysaccharide Receptors - metabolism; Macrophages; Macrophages - pathology; Medical research; Medicine, Experimental; Mice, Inbred C57BL; Mice, Transgenic; microglia; Microglia - pathology; Models, Biological; Monocytes - pathology; Myeloid Cells - metabolism; Neurobiology; Neurons and Cognition; Nitric Oxide Synthase Type II - metabolism; Original; Pathology; Phagocytosis; Phenotype; Plaque, Amyloid - pathology; Rodents; macrophages; cytokines; aging; chemokines; Alzheimer's disease; microglia
• ISSN: 1474-9718; 1474-9726; 1474-9728
• DOI: 10.1111/acel.12522

Summary Alzheimer's disease (AD) is a neurodegenerative disease characterized by formation of amyloid‐β (Aβ) plaques, activated microglia, and neuronal cell death leading to progressive dementia. Recent data indicate that microglia and monocyte‐derived macrophages (MDM) are key players in the initiation and progression of AD, yet their respective roles remain to be clarified. As AD occurs mostly in the elderly and aging impairs myeloid functions, we addressed the inflammatory profile of microglia and MDM during aging in TgAPP/PS1 and TgAPP/PS1dE9, two transgenic AD mouse models, compared to WT littermates. We only found MDM infiltration in very aged mice. We determined that MDM highly expressed activation markers at basal state. In contrast, microglia exhibited an activated phenotype only with normal aging and Aβ pathology. Our study showed that CD14 and CD36, two receptors involved in phagocytosis, were upregulated during Aβ pathogenesis. Moreover, we observed, at the protein levels in AD models, higher production of pro‐inflammatory mediators: IL‐1β, p40, iNOS, CCL‐3, CCL‐4, and CXCL‐1. Taken together, our data indicate that microglia and MDM display distinct phenotypes in AD models and highlight the specific effects of normal aging vs Aβ peptides on inflammatory processes that occur during the disease progression. These precise phenotypes of different subpopulations of myeloid cells in normal and pathologic conditions may allow the design of pertinent therapeutic strategy for AD.