Medial Temporal Lobe Networks in Alzheimer's Disease : Structural and Molecular Vulnerabilities
de Flores, Robin ; Das, Sandhitsu R ; Xie, Long ; Wisse, Laura E M LU
; Lyu, Xueying
; Shah, Preya
; Yushkevich, Paul A
and Wolk, David A
(2022)
In The Journal of Neuroscience : the official journal of the Society for Neuroscience
42(10).
p.2131-2141
- Abstract
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 propagates specifically within the AT and PM networks, and (2) evaluating 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: (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 disease... (More)
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 propagates specifically within the AT and PM networks, and (2) evaluating 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: (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 disease neuroimaging initiative (ADNI)GO/2 to highlight structural covariance patterns (n = 349); and (3) positron emission tomography (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 (BA)35 structurally 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.SIGNIFICANCE STATEMENT The current study provides further support for the notion that two distinct medial temporal lobe (MTL) networks, i.e., anterior-temporal (AT) and the posterior-medial (PM), display differential alterations in the context of Alzheimer's disease (AD). Importantly, neurodegeneration appears to occur within these networks in a dissociable manner marked by their covariance patterns. In addition, the AT and PM networks are also differentially associated with relative tau and amyloid burden, and perhaps differences in the relative burden of tau species [e.g., neurofibriliary tangles (NFTs) vs tau in neuritic plaques]. These findings, in the context of a growing literature consistent with the present results, have important implications for disease spread and the cognitive manifestations of AD in light of the differential cognitive processes ascribed to them.
(Less)
- author
- de Flores, Robin
; Das, Sandhitsu R
; Xie, Long
; Wisse, Laura E M
LU
; Lyu, Xueying
; Shah, Preya
; Yushkevich, Paul A
and Wolk, David A
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer Disease/pathology, Amyloid, Amyloid beta-Peptides/metabolism, Atrophy/pathology, Cognitive Dysfunction/pathology, Female, Humans, Magnetic Resonance Imaging/methods, Male, Positron-Emission Tomography/methods, Temporal Lobe/metabolism, tau Proteins/metabolism
- in
- The Journal of Neuroscience : the official journal of the Society for Neuroscience
- volume
- 42
- issue
- 10
- pages
- 2131 - 2141
- publisher
- Society for Neuroscience
- external identifiers
-
- pmid:35086906
- scopus:85126152501
- ISSN
- 1529-2401
- DOI
- 10.1523/JNEUROSCI.0949-21.2021
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2022 the authors.
- id
- a609421e-5ca5-4b27-875c-d70ea7df3c70
- date added to LUP
- 2022-05-30 13:32:11
- date last changed
- 2024-05-02 00:16:52
@article{a609421e-5ca5-4b27-875c-d70ea7df3c70,
abstract = {{<p>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 propagates specifically within the AT and PM networks, and (2) evaluating 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: (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 disease neuroimaging initiative (ADNI)GO/2 to highlight structural covariance patterns (n = 349); and (3) positron emission tomography (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 (BA)35 structurally 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.SIGNIFICANCE STATEMENT The current study provides further support for the notion that two distinct medial temporal lobe (MTL) networks, i.e., anterior-temporal (AT) and the posterior-medial (PM), display differential alterations in the context of Alzheimer's disease (AD). Importantly, neurodegeneration appears to occur within these networks in a dissociable manner marked by their covariance patterns. In addition, the AT and PM networks are also differentially associated with relative tau and amyloid burden, and perhaps differences in the relative burden of tau species [e.g., neurofibriliary tangles (NFTs) vs tau in neuritic plaques]. These findings, in the context of a growing literature consistent with the present results, have important implications for disease spread and the cognitive manifestations of AD in light of the differential cognitive processes ascribed to them.</p>}},
author = {{de Flores, Robin and Das, Sandhitsu R and Xie, Long and Wisse, Laura E M and Lyu, Xueying and Shah, Preya and Yushkevich, Paul A and Wolk, David A}},
issn = {{1529-2401}},
keywords = {{Alzheimer Disease/pathology; Amyloid; Amyloid beta-Peptides/metabolism; Atrophy/pathology; Cognitive Dysfunction/pathology; Female; Humans; Magnetic Resonance Imaging/methods; Male; Positron-Emission Tomography/methods; Temporal Lobe/metabolism; tau Proteins/metabolism}},
language = {{eng}},
number = {{10}},
pages = {{2131--2141}},
publisher = {{Society for Neuroscience}},
series = {{The Journal of Neuroscience : the official journal of the Society for Neuroscience}},
title = {{Medial Temporal Lobe Networks in Alzheimer's Disease : Structural and Molecular Vulnerabilities}},
url = {{http://dx.doi.org/10.1523/JNEUROSCI.0949-21.2021}},
doi = {{10.1523/JNEUROSCI.0949-21.2021}},
volume = {{42}},
year = {{2022}},
}