Synapses and Dendritic Spines as Pathogenic Targets in Alzheimer’s Disease

Figure 2

A diagram depicting a potential role of glia in mediating the synaptic toxicity of Aβ. Aβ oligomers presumably secreted from the presynaptic neuron could bind to its putative receptor on the postsynaptic cell, and this could then initiate a signaling cascade leading to activation kinases such as MARK, which then acts on tau, PSD-95, and possibly other synaptic substrates to affect AMPAR removal from the synaptic surface, leading to synapse and spine loss. Alternatively, Aβ could act on glial cells near neuronal synapses, which then release factors such as cytokines to activate signaling molecules such as MARK and cause synapse and spine loss. These two mechanisms are not mutually exclusive and could in fact occur simultaneously to mediate Aβ toxicity.