This hypothesis builds on evidence that tau burden relates to age-related cognitive decline (Schöll et al., 2016; Aschenbrenner et al., 2018; Maass et al., 2018), and progression of dementia over 6 to 18 months in patients with Alzheimer’s disease (Koychev et al., 2017; Pontecorvo et al., 2019). Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.