Affiliations: [a] Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA | [b] Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
Correspondence:
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Correspondence to: Joseph El Khoury, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, CNY 149, Room 8301, 149 13th Street, Charlestown, MA 02129, USA. E-mail: [email protected].
Abstract: It is well established that microglia, the neuroimmune cells of the brain, are associated with amyloid-β (Aβ) deposits in Alzheimer's disease (AD). However, the roles of these cells and other mononuclear phagocytes such as monocytes and macrophages in AD pathogenesis and progression have been elusive. Clues to mononuclear phagocyte involvement came with the demonstration that Aβ directly activates microglia and monocytes to produce neurotoxins, signifying that a receptor mediated interaction of Aβ with these cells may be critical for neurodegeneration seen in AD. Also, in AD brain, mononuclear phagocyte distribution changes from a uniform pattern that covers the brain parenchyma to distinct clusters intimately associated with areas of Aβ deposition, but the driving force behind this choreography was unclear. Here, we review our recent work identifying mononuclear phagocyte receptors for Aβ and unraveling mechanisms of recruitment of these cells to areas of Aβ deposition. While our findings and those of others have added significantly to our understanding of the role of the neuroimmune system in AD, the glass remains half full (or half empty) and a lot remains to be uncovered.
