Figure 3.

Neuron-microglia interaction in healthy brain and during Aβ pathology. (a) In a healthy brain, soluble Aβ peptides and small amounts of Aβ seed are cleared by microglia. Microglia receive signals from neurons and secrete neuroprotective factors, control synapse strength, and prune inactive synapses. (b) During Aβ pathology microglia are incapable of removing excessive Aβ aggregates that chronically activate and damage both neurons and microglia. Neurons release excessive neurotransmitters and DAMPs, such as ATP, that further activate microglia. In turn, microglia release inflammatory cytokines that further damage neurons and facilitate Aβ deposition. Aβ-mediated and microglia-mediated insults contribute to neuronal damage, consisting of oxidative stress, reduced axonal transport, weakening of synaptic strength, and excessive elimination of synapses. Abbreviations: DAMP, damage-associated molecular pattern; LTD, long-term depression; LTP, long-term potentiation.