MAPT and early-onset autosomal dominant Alzheimer disease: These findings mirror broader pathology associations with the cortical default mode network40,105 and also align with a recently proposed model of Alzheimer’s disease.39 This model posits a bidirectional relationship between connectivity disruptions within the default mode network and the accumulation of protein pathologies, such as amyloid-beta and tau, with a crucial role of the medial temporal lobe in the intersection of pathologies.