While microglial activation and increased pro-inflammatory cytokine and chemokine expression can initiate or exacerbate ongoing pathology, microglia also perform beneficial actions that limit damage in neurological diseases and conditions. Microglial-mediated processes are a key determinant to the accumulation of amyloid deposits in AD (and its mouse models), playing roles in amyloid degradation (by metalloproteases including neprilysin and insulin degrading enzyme), in removal of amyloid by phagocytosis, and by initiation and growth of plaques (involving seeding by microglial inflammasome activation) [25]. Dysregulation of these processes will alter the balance between amyloid production and clearance, with the net result of increased amyloid burden. In Alzheimer’s disease (AD), microglial phagocytosis of oligomeric and aggregated forms of amyloid beta (Aβ) is one of the key means by which amyloid burden is limited [26, 27]. Several studies suggest that alcohol may be a risk factor for AD [28–31], and there are also reports that alcohol increases amyloid processing and deposition [32–34]. However, whether alcohol influences the ability or efficacy of microglial cells to internalize Aβ has not been examined, although several studies have shown that peripheral macrophages have reduced phagocytotic activity after alcohol treatment [35, 36].
