Astrocytes as mediators of synaptotoxic Abeta-tau interactions in Alzheimer's disease

Synapse loss and cognitive decline in Alzheimer's disease (AD) are correlated with the activation of astrocytes and mislocalisation of tau from the cytosol to synapses (Perez-Nievas et al., 2013). Aggregates of tau are transmitted across synapses in a neuronal activity-dependent manner, and these spread through diseased brain along anatomically connected pathways. The presence of this tau pathology underlies the synaptic dysfunction and neuron loss observed as AD progresses. Astrocytes are intrinsic components of tripartite synapses and play a role in basal synaptic functions, prompting speculation that astrocytes might play a role in the spread of tau pathology. We have previously shown that astrocytes can modulate the effects of A beta on tau (Garwood et al., 2011), and this is likely to have important consequences for tau transmission in AD.