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      M2b macrophage subset decrement as an indicator of cognitive function in Alzheimer's disease

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          Macrophage activation and polarization

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            Macrophage polarization in pathology.

            Macrophages are cells of the innate immunity constituting the mononuclear phagocyte system and endowed with remarkable different roles essential for defense mechanisms, development of tissues, and homeostasis. They derive from hematopoietic precursors and since the early steps of fetal life populate peripheral tissues, a process continuing throughout adult life. Although present essentially in every organ/tissue, macrophages are more abundant in the gastro-intestinal tract, liver, spleen, upper airways, and brain. They have phagocytic and bactericidal activity and produce inflammatory cytokines that are important to drive adaptive immune responses. Macrophage functions are settled in response to microenvironmental signals, which drive the acquisition of polarized programs, whose extremes are simplified in the M1 and M2 dichotomy. Functional skewing of monocyte/macrophage polarization occurs in physiological conditions (e.g., ontogenesis and pregnancy), as well as in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer) and is now considered a key determinant of disease development and/or regression. Here, we will review evidence supporting a dynamic skewing of macrophage functions in disease, which may provide a basis for macrophage-centered therapeutic strategies.
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              Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies.

              Alzheimer's disease (AD) lesions are characterized by the presence of numerous inflammatory proteins. This has led to the hypothesis that brain inflammation is a cause of neuronal injury in AD and that anti-inflammatory drugs may act as protective agents. Seventeen epidemiologic studies from nine different countries have now been published in which arthritis, a major indication for the use of anti-inflammatory drugs, or anti-inflammatory drugs themselves have been considered as risk factors for AD. Both factors appear to be associated with a reduced prevalence of AD. The small size of most studies has limited their individual statistical significance, but similarities in design have made it possible to evaluate combined results. We have used established methods of statistical meta-analysis to estimate the overall chance of individuals exposed to arthritis or anti-inflammatory drugs developing AD as compared with the general population. Seven case-control studies with arthritis as the risk factor yielded an overall odds ratio of 0.556 (p < 0.0001), while four case-control studies with steroids yielded odds ratios of 0.656 (p = 0.049) and three case-control studies with nonsteroidal anti-inflammatory drugs (NSAIDs) yielded an odds ratio of 0.496 (p = 0.0002). When NSAIDs and steroids were combined into a single category of anti-inflammatory drugs, the odds ratio was 0.556 (p < 0.0001). Population-based studies were less similar in design than case-control studies, complicating the process of applying statistical meta-analytical techniques. Nevertheless, population-based studies with rheumatoid arthritis and NSAID use as risk factors strongly supported the results of case-control studies. These data suggest anti-inflammatory drugs may have a protective effect against AD. Controlled clinical trials will be necessary to test this possibility.

                Author and article information

                (View ORCID Profile)
                Psychiatry and Clinical Neurosciences
                Psychiatry Clin. Neurosci.
                July 2020
                April 28 2020
                July 2020
                : 74
                : 7
                : 383-391
                [1 ]Department of NeurologyKaohsiung Municipal Hsiao‐Kang Hospital, Kaohsiung Medical University Kaohsiung Taiwan
                [2 ]Department of NeurologyKaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung Taiwan
                [3 ]Neuroscience Research CenterKaohsiung Medical University Kaohsiung Taiwan
                [4 ]Department of NeurologyKaohsiung Municipal Ta‐Tung Hospital, Kaohsiung Medical University Hospital Kaohsiung Taiwan
                [5 ]Department of PediatricsKaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung Taiwan
                [6 ]Department of Pediatrics, Faculty of PediatricsCollege of Medicine, Kaohsiung Medical University Kaohsiung Taiwan
                [7 ]Graduate Institute of Medicine, College of MedicineKaohsiung Medical University Kaohsiung Taiwan
                [8 ]Department of PediatricsKaohsiung Municipal Hsiao‐Kang Hospital Kaohsiung Taiwan
                [9 ]Department of and Masterʼs Program in Neurology, Faculty of MedicineKaohsiung Medical University Kaohsiung Taiwan
                [10 ]Chinese Mentality Protection Association Kaohsiung Taiwan
                © 2020




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