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. Author manuscript; available in PMC: 2015 Jan 7.
Published in final edited form as: Neuron. 2014 Nov 5;84(3):608–622. doi: 10.1016/j.neuron.2014.10.038

Figure 4.

Figure 4

Hypothetical model of the interaction of amyloid-β (Aβ) and tau accumulation. Advancing age is nearly ubiquitously associated with the gradual accumulation of Tau aggregates in medial temporal lobe (MTL), but it remains unknown whether MTL tau in isolation is associated with “age-related cognitive change. Age and genetics influence likelihood of accumulating elevated levels of amyloid-β (Aβ) aggregates. Aβ is hypothesized to increase the accumulation of Tau aggregates and in particular to accelerate the spread of Tau out of the MTL into the neocortex through local diffusion and perhaps via transynaptic spread across neural networks. Tau accumulation leads to synaptic dysfunction, glial activation, and eventually neuronal loss. Aβ may also have direct synaptic toxicity that is not mediated through Tau. The spreading of Tau into neocortex and associated neurodegenerative processes are thought to result in cognitive impairment and further progression along the clinical trajectory of Alzheimer’s disease.