Journal Article

DZNE-2025-00023

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Increasing hub disruption parallels dementia severity in autosomal dominant Alzheimer's disease.

Tu, J. C. ; Millar, P. R. ; Strain, J. F. ; Eck, A. ; Adeyemo, B. ; Snyder, A. Z. ; Daniels, A. ; Karch, C. ; Huey, E. D. ; McDade, E. ; Day, G. S. ; Yakushev, I. ; Hassenstab, J. ; Morris, J. ; Llibre-Guerra, J. J. ; Ibanez, L. ; Jucker, M.DZNE* ; Mendez, P. C. ; Perrin, R. J. ; Benzinger, T. L. S. ; Jack, C. R. ; Betzel, R. ; Ances, B. M. ; Eggebrecht, A. T. ; Gordon, B. A. ; Wheelock, M. D. ; Network, D. I. A. (Collaboration Author)

2024
The MIT Press Cambridge, MA

This record in other databases:    

Please use a persistent id in citations: doi:10.1162/netn_a_00395

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.

Keyword(s): Alzheimer’s disease ; Biomarker ; Functional connectivity ; Hubs ; Neurodegeneration

---

Contributing Institute(s):

1. Cell Biology of Neurological Diseases (AG Jucker)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

---

Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---

---

Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article (Erratum/Correction) Tu, J. C. ; Millar, P. R. ; Strain, J. F. ; Eck, A. ; Adeyemo, B. ; Snyder, A. Z. ; Daniels, A. ; Karch, C. ; Huey, E. D. ; McDade, E. ; Day, G. S. ; Yakushev, I. ; Hassenstab, J. ; Morris, J. ; Llibre-Guerra, J. J. ; Ibanez, L. ; Jucker, M.DZNE* ; Mendez, P. C. ; Perrin, R. J. ; Benzinger, T. L. S. ; Jack, C. R. ; Betzel, R. ; Ances, B. M. ; Eggebrecht, A. T. ; Gordon, B. A. ; Wheelock, M. D. ; Network, D. I. A. (Collaboration Author)
Erratum: Increasing hub disruption parallels dementia severity in autosomal dominant Alzheimer's disease.
Network neuroscience 9(1), i (2025) [10.1162/netn_x_00462]2025   Files  Fulltext by Pubmed Central BibTeX | EndNote: XML, Text | RIS

---