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000274042 1001_ $$00000-0003-1982-9890$$aTu, Jiaxin Cindy$$b0
000274042 245__ $$aIncreasing hub disruption parallels dementia severity in autosomal dominant Alzheimer's disease.
000274042 260__ $$aCambridge, MA$$bThe MIT Press$$c2024
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000274042 520__ $$aHub 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.
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000274042 650_7 $$2Other$$aAlzheimer’s disease
000274042 650_7 $$2Other$$aBiomarker
000274042 650_7 $$2Other$$aFunctional connectivity
000274042 650_7 $$2Other$$aHubs
000274042 650_7 $$2Other$$aNeurodegeneration
000274042 7001_ $$aMillar, Peter R$$b1
000274042 7001_ $$aStrain, Jeremy F$$b2
000274042 7001_ $$aEck, Andrew$$b3
000274042 7001_ $$aAdeyemo, Babatunde$$b4
000274042 7001_ $$aSnyder, Abraham Z$$b5
000274042 7001_ $$aDaniels, Alisha$$b6
000274042 7001_ $$aKarch, Celeste$$b7
000274042 7001_ $$aHuey, Edward D$$b8
000274042 7001_ $$aMcDade, Eric$$b9
000274042 7001_ $$aDay, Gregory S$$b10
000274042 7001_ $$aYakushev, Igor$$b11
000274042 7001_ $$aHassenstab, Jason$$b12
000274042 7001_ $$aMorris, John$$b13
000274042 7001_ $$aLlibre-Guerra, Jorge J$$b14
000274042 7001_ $$aIbanez, Laura$$b15
000274042 7001_ $$0P:(DE-2719)2000010$$aJucker, Mathias$$b16$$udzne
000274042 7001_ $$aMendez, Patricio Chrem$$b17
000274042 7001_ $$aPerrin, Richard J$$b18
000274042 7001_ $$aBenzinger, Tammie L S$$b19
000274042 7001_ $$aJack, Clifford R$$b20
000274042 7001_ $$aBetzel, Richard$$b21
000274042 7001_ $$aAnces, Beau M$$b22
000274042 7001_ $$aEggebrecht, Adam T$$b23
000274042 7001_ $$aGordon, Brian A$$b24
000274042 7001_ $$00000-0002-3409-8777$$aWheelock, Muriah D$$b25
000274042 7001_ $$aNetwork, Dominantly Inherited Alzheimer$$b26$$eCollaboration Author
000274042 773__ $$0PERI:(DE-600)2900481-0$$a10.1162/netn_a_00395$$gVol. 8, no. 4, p. 1265 - 1290$$n4$$p1265 - 1290$$tNetwork neuroscience$$v8$$x2472-1751$$y2024
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