Fig. 2.

Putative pathophysiological mechanisms for dendritic spine loss. 1 Fibrillar amyloid plaques cause spine loss in their immediate vicinity. 2 Spine loss at dystrophic dendrites. 3 Secondary spine loss due to presynaptic failure. 4 Amyloid oligomers engaging synaptic targets. 5 Amyloid uptake. 6 Axonal amyloid beta. 7 Hyperphosphorylated tau protein. 8 Deafferentation. 9 NMDA receptor-mediated excitotoxicity. 10 Spine pruning by microglia; Microglia activation leading to release of inflammatory mediators. 11 Immune activation, reactive oxygen species and activation of pro-apoptotic pathways