In addition to neuron activity-dependent tau secretion, the extracellular form of the protein may arise by other mechanisms, such as neuron death (Gomez-Ramos et al., 2006), intracellular tau accumulation (Simon et al., 2012), a tauopathy (Clavaguera et al., 2009), or modulation by tau mutations (Karch et al., 2012). This evidence concerns the gene MAPT and tauopathy.