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An Artificial Intelligence-Driven Multimorbidity Framework Reveals a Shared Metabolic and Immune Core Across Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia
Meghna R. Iyer, Benjamin Zhao, Xin He, David Camacho, Zihan Wei, Jennifer H. Deng, Cassie S. Mitchell. Biomedicines, 2026-02-16
Topic: Amyloid, tau and blood-test diagnosis
Across AD, ALS, and FTD, a convergent multimorbidity architecture centered on a shared metabolic and immune core was identified, accompanied by prominent neurobehavioral processes and intermediate systems including gastrointestinal, endocrine, hematological, hepatic, and sensory pathways. Disease-specific signatures shaped distinct vulnerability profiles within this shared structure, including cardiovascular enrichment in AD, neuromuscular and toxin-related pathways in ALS, and coupled neurobehavioral–metabolic features in FTD. PHSU patterns reinforced these findings, with centrally positioned compounds predominantly targeting inflammatory, metabolic, or neuromodulatory processes. These findings position AD, ALS, and FTD within a unified, AI-derived multimorbidity framework. This ontology-guided approach provides a computational, hypothesis-generating foundation for multimorbidity-aware biomarker discovery, risk stratification, and cross-disease therapeutic exploration in neurodegenerative disease.
Key findings
- Across AD, ALS, and FTD, a convergent multimorbidity architecture centered on a shared metabolic and immune core was identified, accompanied by prominent neurobehavioral processes and intermediate systems including gastrointestinal, endocrine, hematological, hepatic, and sensory pathways.
- Disease-specific signatures shaped distinct vulnerability profiles within this shared structure, including cardiovascular enrichment in AD, neuromuscular and toxin-related pathways in ALS, and coupled neurobehavioral–metabolic features in FTD.
- PHSU patterns reinforced these findings, with centrally positioned compounds predominantly targeting inflammatory, metabolic, or neuromodulatory processes.
- These findings position AD, ALS, and FTD within a unified, AI-derived multimorbidity framework.
- This ontology-guided approach provides a computational, hypothesis-generating foundation for multimorbidity-aware biomarker discovery, risk stratification, and cross-disease therapeutic exploration in neurodegenerative disease.
Why it matters
This computational study identifies a shared metabolic and immune core across Alzheimer's disease, ALS and frontotemporal dementia, providing a hypothesis-generating foundation for biomarker discovery and cross-disease therapeutic exploration. It is a computational analysis only and does not test any treatment, cure or prevention.
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Study details
- Evidence strengthLow
How this study scored 38/100
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 (Biomedicines) |
| Journal's citation record | 1 / 4 | Biomedicines: journal h-index 133 (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 | 5 / 5 | 2026 — within 1 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 | 1 / 7 | Cited 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 9.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Cassie S. Mitchell: h-index 23 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Emory University: institution h-index 1,360 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41751343) |
| Free to read | 2 / 2 | Free to read |
| Total | 38 / 100 | — |
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Read the original
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. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Iyer, M. R., Zhao, B., He, X., Camacho, D., Wei, Z., Deng, J. H., et al. (2026). An Artificial Intelligence-Driven Multimorbidity Framework Reveals a Shared Metabolic and Immune Core Across Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia. Biomedicines. https://doi.org/10.3390/biomedicines14020444
Vancouver
Iyer MR, Zhao B, He X, Camacho D, Wei Z, Deng JH, et al. An Artificial Intelligence-Driven Multimorbidity Framework Reveals a Shared Metabolic and Immune Core Across Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia. Biomedicines. 2026. doi:10.3390/biomedicines14020444. PMID: 41751343.
BibTeX
@article{iyer2026-41751343,
author = {Iyer, Meghna R. and Zhao, Benjamin and He, Xin and Camacho, David and Wei, Zihan and Deng, Jennifer H. and Mitchell, Cassie S.},
title = {{An Artificial Intelligence-Driven Multimorbidity Framework Reveals a Shared Metabolic and Immune Core Across Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia}},
journal = {Biomedicines},
year = {2026},
doi = {10.3390/biomedicines14020444},
pmid = {41751343},
url = {https://doi.org/10.3390/biomedicines14020444}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.