Ultimately, it is likely that both spread and susceptibility play a part in neurodegeneration, but have different roles in different disorders; for example we have used functional connectivity and PET to examine the distribution of tau in neurodegeneration, finding that the pattern in Alzheimer’s disease was more in keeping with trans-synaptic spread, and in PSP was more in keeping with susceptibility of metabolically active regions [57]. The gene discussed is MAPT; the disease is early-onset autosomal dominant Alzheimer disease.