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Data-Driven Modeling of Amyloid-beta Targeted Antibodies for Alzheimer’s Disease
Rabiei K, Petrella JR, Lenhart S, Liu C, Doraiswamy PM, Hao W.. NPJ systems biology and applications, 2025-04-03
Topic: Drug trials: efficacy and safety
Alzheimer’s disease (AD) is caused by the build-up of amyloid beta (A$\beta$) proteins in the brain, leading to memory loss and cognitive decline. Despite the approval of monoclonal antibodies targeting A$\beta$, optimizing treatment strategies while minimizing side effects remains a challenge. This study develops a mathematical framework to model A$\beta$ aggregation dynamics, capturing the transition from monomers to higher-order aggregates, including protofibrils, toxic oligomers, and fibrils, using mass-action kinetics and coarse-grained modeling. Parameter estimation, sensitivity analysis, and data-driven calibration ensure model robustness. An optimal control framework is introduced to identify the optimal dose of the drug as a control function that reduces toxic oligomers and fibrils while minimizing adverse effects, such as amyloid-related imaging abnormalities (ARIA). The results indicate that Donanemab achieves the most significant reduction in fibrils. These findings provide a quantitative basis for optimizing AD treatments, providing valuable insight into the balance between therapeutic efficacy and safety.
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APA 7th
Rabiei, K., Petrella, JR., Lenhart, S., Liu, C., Doraiswamy, P. M., & Hao, W. (2025). Data-Driven Modeling of Amyloid-beta Targeted Antibodies for Alzheimer’s Disease. NPJ systems biology and applications. https://doi.org/10.21203/rs.3.rs-6316455/v1
Vancouver
Rabiei K, Petrella JR, Lenhart S, Liu C, Doraiswamy PM, Hao W. Data-Driven Modeling of Amyloid-beta Targeted Antibodies for Alzheimer’s Disease. NPJ systems biology and applications. 2025. doi:10.21203/rs.3.rs-6316455/v1.
BibTeX
@article{rabiei2025-32628a51,
author = {Rabiei, K. and Petrella, JR. and Lenhart, S. and Liu, C. and Doraiswamy, P. M. and Hao, W.},
title = {{Data-Driven Modeling of Amyloid-beta Targeted Antibodies for Alzheimer’s Disease}},
journal = {NPJ systems biology and applications},
year = {2025},
doi = {10.21203/rs.3.rs-6316455/v1},
url = {https://doi.org/10.21203/rs.3.rs-6316455/v1}
}
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Key findings
- The results indicate that Donanemab achieves the most significant reduction in fibrils.
- These findings provide a quantitative basis for optimizing AD treatments, providing valuable insight into the balance between therapeutic efficacy and safety.
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Study details
- Evidence strengthLow
How this study scored 40/100
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. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 23 of the 58 points we could judge it on, which is 40 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (NPJ systems biology and applications) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 4 / 5 | 2025 — within 3 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 23 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 58 points we could judge it on is 40 out of 100. |
| Total | 40 / 100 | — |
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