Medial Temporal Lobe Networks in Alzheimer's Disease: Structural and Molecular Vulnerabilities

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 (1) investigating whether MTL atrophy pmpagates specifically within the AT and PM networks, and (2) evaluating the vulnerability of these networks to AD pmteinopathies. To do that, we used neuroimaging data acquired in human male and female in three distinct cohorts: (1) resting-state functional MRI (rs-fMRI) from the aging brain cohort (ABC) to define the AT and PM networks (n=68); (2) longitudinal structural MRI from Alzheimer's diseaw neuroimaging initiative (ADNI)GO/2 to highlight structural covariance patterns (n = 349); and (3) positron emission tomography (PET) data from ADN13 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 (BA)35 stnicturally covaried within the AT network while the parahippocampal cortex (PHC) covaried within the PM network. In addition, these networks are differentially associated with relative tau and amyloid burden, with higher tau levels in AT than in PM and higher amyloid levels in PM than in AT. our results also suggest differences in the relative burden of tau species. The current results provide further support for the notion that two distinct MTL networks display differential alterations in the context of AD. These findings have important implications for disease spread and the cognitive manifestations of AD.

Automated summary

This study reveals the relationship between the medial temporal lobe and the anterior-temporal and posterior-medial networks, and explores the vulnerability of these networks to proteinopathies in Alzheimer's disease. The results show that the atrophy of distinct subregions in the medial temporal lobe propagates differently within the anterior-temporal and posterior-medial networks. Additionally, these networks are differentially associated with relative tau and amyloid burden.