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Transcriptome-informed metabolic modeling reveals astrocyte-specific vulnerabilities in mild cognitive impairment and Alzheimer’s disease progression
Andrea Angarita-Rodríguez, Viviana Vargas-López, Andres Pinzón, Adrián Sandoval-Hernandez, Kai Kang, Leping Li, Jason Papin, Pedro Puentes-Rozo et al.. Frontiers in Bioinformatics, 2026-06-02
Topic: Brain proteins, microglia and lab models
The analyses supported stage-dependent remodeling of astrocyte-associated transcriptional and metabolic programs during disease progression. Early MCI was associated with signaling and stress-adaptation changes, whereas advanced MCI and AD showed broader disruption of synaptic support, redox homeostasis, and inflammatory-related programs. Model predictions indicated a progressive reduction in a biomass-derived maintenance proxy from control to advanced MCI, followed by a partial rebound in AD, suggesting a compensatory shift toward reactive-like astrocyte states rather than full functional recovery. Flux variability analysis revealed reduced metabolic flexibility across disease stages, particularly in glutamate-glutamine cycling, glutathione/redox metabolism, glycolysis-pyruvate metabolism, cholesterol handling, and one-carbon/folate metabolism. These findings support the view that astrocytes undergo progressive, stage-specific metabolic reprogramming during the transition from healthy aging to AD. Early alterations in redox regulation, neurotransmitter cycling, and mitochondrial function may contribute to early neuronal vulnerability. This work highlights astrocyte-centered pathways as potential targets for future experimental validation and therapeutic exploration.
Key findings
- The analyses supported stage-dependent remodeling of astrocyte-associated transcriptional and metabolic programs during disease progression.
- Early MCI was associated with signaling and stress-adaptation changes, whereas advanced MCI and AD showed broader disruption of synaptic support, redox homeostasis, and inflammatory-related programs.
- Model predictions indicated a progressive reduction in a biomass-derived maintenance proxy from control to advanced MCI, followed by a partial rebound in AD, suggesting a compensatory shift toward reactive-like astrocyte states rather than full functional recovery.
- Flux variability analysis revealed reduced metabolic flexibility across disease stages, particularly in glutamate-glutamine cycling, glutathione/redox metabolism, glycolysis-pyruvate metabolism, cholesterol handling, and one-carbon/folate metabolism.
- These findings support the view that astrocytes undergo progressive, stage-specific metabolic reprogramming during the transition from healthy aging to AD.
Why it matters
This transcriptome-informed metabolic modeling study found stage-specific metabolic reprogramming in astrocytes during progression from mild cognitive impairment to Alzheimer's disease and highlighted astrocyte-centered pathways as potential targets for future research. It is a modeling study and does not test any treatment, cure, or prevention.
Study details
- Evidence strengthLow
How this study scored 36/100
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 (Frontiers in Bioinformatics) |
| Journal's citation record | 0 / 4 | Frontiers in Bioinformatics: journal h-index 33 (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 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.2× 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 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Janneth González: h-index 28 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Virginia: institution h-index 1,118 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42311824) |
| Free to read | 2 / 2 | Free to read |
| Total | 36 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fbinf.2026.1816121
- PubMed: 42311824
- Original source →
- Free full text: Frontiers in Bioinformatics →
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Angarita-Rodríguez, A., Vargas-López, V., Pinzón, A., Sandoval-Hernandez, A., Kang, K., Li, L., et al. (2026). Transcriptome-informed metabolic modeling reveals astrocyte-specific vulnerabilities in mild cognitive impairment and Alzheimer’s disease progression. Frontiers in Bioinformatics. https://doi.org/10.3389/fbinf.2026.1816121
Vancouver
Angarita-Rodríguez A, Vargas-López V, Pinzón A, Sandoval-Hernandez A, Kang K, Li L, et al. Transcriptome-informed metabolic modeling reveals astrocyte-specific vulnerabilities in mild cognitive impairment and Alzheimer’s disease progression. Frontiers in Bioinformatics. 2026. doi:10.3389/fbinf.2026.1816121. PMID: 42311824.
BibTeX
@article{angaritarodriguez2026-42311824,
author = {Angarita-Rodríguez, Andrea and Vargas-López, Viviana and Pinzón, Andres and Sandoval-Hernandez, Adrián and Kang, Kai and Li, Leping and Papin, Jason and Puentes-Rozo, Pedro and others},
title = {{Transcriptome-informed metabolic modeling reveals astrocyte-specific vulnerabilities in mild cognitive impairment and Alzheimer’s disease progression}},
journal = {Frontiers in Bioinformatics},
year = {2026},
doi = {10.3389/fbinf.2026.1816121},
pmid = {42311824},
url = {https://doi.org/10.3389/fbinf.2026.1816121}
}
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