A further, potentially related, factor is the role of pervasive patterns of activity in circuit function and in predisposing networks to the effects of neurodegenerative disease [55]: examples include the differential and possibly use-dependent susceptibility of particular motor pools to amyotrophic lateral sclerosis (ALS) [27], or the altered trafficking of amyloid and tau in the isodendritic core associated with perturbations of the sleep–wake cycle in AD [56]. The gene discussed is MAPT; the disease is neurodegenerative disease.