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@ARTICLE{Tu:274042,
author = {Tu, Jiaxin Cindy and Millar, Peter R and Strain, Jeremy F
and Eck, Andrew and Adeyemo, Babatunde and Snyder, Abraham Z
and Daniels, Alisha and Karch, Celeste and Huey, Edward D
and McDade, Eric and Day, Gregory S and Yakushev, Igor and
Hassenstab, Jason and Morris, John and Llibre-Guerra, Jorge
J and Ibanez, Laura and Jucker, Mathias and Mendez, Patricio
Chrem and Perrin, Richard J and Benzinger, Tammie L S and
Jack, Clifford R and Betzel, Richard and Ances, Beau M and
Eggebrecht, Adam T and Gordon, Brian A and Wheelock, Muriah
D},
collaboration = {Network, Dominantly Inherited Alzheimer},
title = {{I}ncreasing hub disruption parallels dementia severity in
autosomal dominant {A}lzheimer's disease.},
journal = {Network neuroscience},
volume = {8},
number = {4},
issn = {2472-1751},
address = {Cambridge, MA},
publisher = {The MIT Press},
reportid = {DZNE-2025-00023},
pages = {1265 - 1290},
year = {2024},
abstract = {Hub regions in the brain, recognized for their roles in
ensuring efficient information transfer, are vulnerable to
pathological alterations in neurodegenerative conditions,
including Alzheimer's disease (AD). Computational
simulations and animal experiments have hinted at the theory
of activity-dependent degeneration as the cause of this hub
vulnerability. However, two critical issues remain
unresolved. First, past research has not clearly
distinguished between two scenarios: hub regions facing a
higher risk of connectivity disruption (targeted attack) and
all regions having an equal risk (random attack). Second,
human studies offering support for activity-dependent
explanations remain scarce. We refined the hub disruption
index to demonstrate a hub disruption pattern in functional
connectivity in autosomal dominant AD that aligned with
targeted attacks. This hub disruption is detectable even in
preclinical stages, 12 years before the expected symptom
onset and is amplified alongside symptomatic progression.
Moreover, hub disruption was primarily tied to regional
differences in global connectivity and sequentially followed
changes observed in amyloid-beta positron emission
tomography cortical markers, consistent with the
activity-dependent degeneration explanation. Taken together,
our findings deepen the understanding of brain network
organization in neurodegenerative diseases and could be
instrumental in refining diagnostic and targeted therapeutic
strategies for AD in the future.},
keywords = {Alzheimer’s disease (Other) / Biomarker (Other) /
Functional connectivity (Other) / Hubs (Other) /
Neurodegeneration (Other)},
cin = {AG Jucker},
ddc = {610},
cid = {I:(DE-2719)1210001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39735502},
pmc = {pmc:PMC11674321},
doi = {10.1162/netn_a_00395},
url = {https://pub.dzne.de/record/274042},
}