The medial temporal lobe (MTL) is connected to the rest of the brain through two main networks: the anterior-temporal (AT) and the posterior-medial (PM) systems. Given the crucial role of the MTL and networks in the physiopathology of Alzheimer’s Disease (AD), the present study aimed at i) investigate whether MTL atrophy propagates specifically within the AT and PM networks, and ii) evaluate the vulnerability of these networks to AD proteinopathies. To do that, we used neuroimaging data acquired in human male and female in three distinct cohorts: i) resting-state functional MRI from the Aging Brain Cohort to define the AT and PM networks (n=68), ii) longitudinal structural MRI from ADNIGO/2 to highlight structural covariance patterns (n=349), and iii) PET data from ADNI3 to evaluate the networks’ vulnerability to amyloid and tau (n=186). Our results suggest that the atrophy of distinct MTL subregions propagates within the AT and PM networks in a dissociable manner. Brodmann Area 35 structurally covaried ...