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Activity dependent degeneration explains hub vulnerability in Alzheimer's disease
de Haan W, Mott K, van Straaten EC, Scheltens P, Stam CJ.. PLoS computational biology, 2012-08-16
Topic: Amyloid, tau and blood-test diagnosis
Brain connectivity studies have revealed that highly connected 'hub' regions are particularly vulnerable to Alzheimer pathology: they show marked amyloid-β deposition at an early stage. Recently, excessive local neuronal activity has been shown to increase amyloid deposition. In this study we use a computational model to test the hypothesis that hub regions possess the highest level of activity and that hub vulnerability in Alzheimer's disease is due to this feature. Cortical brain regions were modeled as neural masses, each describing the average activity (spike density and spectral power) of a large number of interconnected excitatory and inhibitory neurons. The large-scale network consisted of 78 neural masses, connected according to a human DTI-based cortical topology. Spike density and spectral power were positively correlated with structural and functional node degrees, confirming the high activity of hub regions, also offering a possible explanation for high resting state Default Mode Network activity. 'Activity dependent degeneration' (ADD) was simulated by lowering synaptic strength as a function of the spike density of the main excitatory neurons, and compared to random degeneration. Resulting structural and functional network changes were assessed with graph theoretical analysis. Effects of ADD included oscillatory slowing, loss of spectral power and long-range synchronization, hub vulnerability, and disrupted functional network topology. Observed transient increases in spike density and functional connectivity match reports in Mild Cognitive Impairment (MCI) patients, and may not be compensatory but pathological. In conclusion, the assumption of excessive neuronal activity leading to degeneration provides a possible explanation for hub vulnerability in Alzheimer's disease, supported by the observed relation between connectivity and activity and the reproduction of several neurophysiologic hallmarks. The insight that neuronal activity might play a causal role in Alzheimer's disease can have implications for early detection and interventional strategies.
Key findings
- Brain connectivity studies have revealed that highly connected 'hub' regions are particularly vulnerable to Alzheimer pathology: they show marked amyloid-β deposition at an early stage.
- Spike density and spectral power were positively correlated with structural and functional node degrees, confirming the high activity of hub regions, also offering a possible explanation for high resting state Default Mode Network activity. 'Activity dependent degeneration' (ADD) was simulated by lowering synaptic strength as a function of the spike density of the main excitatory neurons, and compared to random degeneration.
- In conclusion, the assumption of excessive neuronal activity leading to degeneration provides a possible explanation for hub vulnerability in Alzheimer's disease, supported by the observed relation between connectivity and activity and the reproduction of several neurophysiologic hallmarks.
Why it matters
A computer model suggested that highly connected brain hub regions have the highest activity and that this activity could explain their vulnerability to Alzheimer pathology. This is a simulation, not a study in people, so it does not establish a treatment or prevention.
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Study details
- Evidence strengthLow
How this study scored 50/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (PLoS computational biology) |
| Journal's citation record | 3 / 4 | PLoS Computational Biology: journal h-index 282 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 393 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 24.6 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 4 / 6 | Cited 15.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 3 / 4 | Cited 63 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Cornelis J. Stam: h-index 108 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Amsterdam UMC Location Vrije Universiteit Amsterdam: institution h-index 938 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22915996) |
| Free to read | 2 / 2 | Free to read |
| Total | 50 / 100 | — |
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Read the original
- DOI: 10.1371/journal.pcbi.1002582
- PubMed: 22915996
- Original source →
- Free full text: PLoS Computational Biology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
de Haan, W., Mott, K., van Straaten, E. C., Scheltens, P., & Stam, C. J. (2012). Activity dependent degeneration explains hub vulnerability in Alzheimer's disease. PLoS computational biology. https://doi.org/10.1371/journal.pcbi.1002582
Vancouver
de Haan W, Mott K, van Straaten EC, Scheltens P, Stam CJ. Activity dependent degeneration explains hub vulnerability in Alzheimer's disease. PLoS computational biology. 2012. doi:10.1371/journal.pcbi.1002582. PMID: 22915996.
BibTeX
@article{dehaan2012-22915996,
author = {de Haan, W. and Mott, K. and van Straaten, E. C. and Scheltens, P. and Stam, C. J.},
title = {{Activity dependent degeneration explains hub vulnerability in Alzheimer's disease}},
journal = {PLoS computational biology},
year = {2012},
doi = {10.1371/journal.pcbi.1002582},
pmid = {22915996},
url = {https://doi.org/10.1371/journal.pcbi.1002582}
}
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6 studies in the alzhub library list this one in their references.