The Ambiguous Role of Microglia in Aß Toxicity: Chances for Therapeutic Intervention.

Amyloid-ß (Aß) has long been shown to be critical in Alzheimer's disease pathophysiology. Microglia contributes to the earliest responses to Aß buildup, by direct interaction through multiple receptors. Microglial cells operate Aß clearance and trigger inflammatory/regenerative processes that take place in the long years of silent disease progression that precede symptomatic appearance. But in time and with aging, the fine balance between pro- and anti-inflammatory activity of microglia deranges, negatively impacting its Aß-clearing ability. Furthermore, in recent years, microglial activation has proven to be much more complex than the mere dichotomic pro/antiinflammatory polarization previously accepted. Microglia can display a wide spectrum of phenotypes, which can even be mixed. On these bases, it is evident that while pharmacological intervention aiding microglia to prolong its ability to cope with Aß buildup could be extremely relevant, its feasibility is hampered by such high complexity, which still needs to be completely understood.