Fig.1.

Increased microglial reactivity or increased protein clearance may reduce microglial synaptic maintenance. (1) Microglia monitor and prune CNS synapses throughout life in conjunction with peri-synaptic astrocytes. Microglia also phagocytose small amounts of extracellular protein such as Aβ, although it is not yet known whether microglia perform both phagocytic tasks simultaneously. Dysfunctional microglial activity at the synapse may produce one of the two following scenarios. (2) Increased pro-inflammatory activation of microglia results in increased production of inflammatory cytokines, co-activating peri-synaptic astrocytes, resulting in neuronal excitability and degeneration. (3) Alternatively, increased demands on microglial phagocytosis, such as elevated Aβ production, may reduce synaptic maintenance and result in increased Aβ at the synapse.