The initial increase in excitability and connectivity tied to the incipient Aβ pathology later leads to a state of hypoexcitability, associated with tau accumulation and neuronal death.7,9,11,12 Similarly, a previous study from our group52 described an initial longitudinal increase in connectivity in key regions for Alzheimer’s disease among first-degree relatives, who also showed a positive correlation between their FC values and p-tau231. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.