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Closed-head injury produces a delayed, region-specific defect in glucose-carbon routing at the pyruvate branchpoint in APP/PS1 KI mice
Moallem EZ, Bruntz RC, Cox MF, Bytyqi L, Roberts TK, Patel SP, Macheda T, Roberts KN et al.. bioRxiv, 2026-10-06
Topic: Gut, metabolism and diet
Traumatic brain injury (TBI) is a risk factor for Alzheimer’s disease (AD), and both conditions are associated with impaired glucose metabolism and mitochondrial dysfunction. We previously reported time-dependent mitochondrial dysfunction following closed-head injury (CHI) in amyloid precursor protein/presenilin 1 (APP/PS1) knock-in (KI) mice, but whether glucose-derived carbon labeling showed a corresponding temporal pattern remained unknown. We hypothesized that early deficits would involve tricarboxylic acid (TCA)-cycle metabolites, whereas chronic changes persisted upstream at the pyruvate-lactate branchpoint. Here, oral uniformly 13 C-labeled glucose ([U- 13 C]-glucose) tracing and gas chromatography-mass spectrometry (GC-MS)-based isotopologue analysis were used to quantify first-turn glucose-derived carbon fate in cortex and hippocampus. To distinguish the effects of age at injury from those of post-injury interval, mice were analyzed 1 month after injury either at 7 or 12 months of age or 8 months after injury at 12 months of age. The most pronounced alterations occurred 8 months after CHI, when KI mice exhibited increased pyruvate and lactate labeling in the cortex and broader increases in glycolytic labeling in the hippocampus. These findings suggest that in APP/PS1 KI mice, chronic closed-head injury produced a delayed shift in glucose-derived carbon labeling centered on glycolytic and pyruvate/lactate nodes, with loss of hippocampal precursor-product coupling but without broad reduction of first-turn TCA-linked labeling. Graphical abstract
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APA 7th
Moallem, E. Z., Bruntz, R. C., Cox, M. F., Bytyqi, L., Roberts, T. K., Patel, S. P., et al. (2026). Closed-head injury produces a delayed, region-specific defect in glucose-carbon routing at the pyruvate branchpoint in APP/PS1 KI mice. bioRxiv. https://doi.org/10.64898/2026.09.29.755475
Vancouver
Moallem EZ, Bruntz RC, Cox MF, Bytyqi L, Roberts TK, Patel SP, et al. Closed-head injury produces a delayed, region-specific defect in glucose-carbon routing at the pyruvate branchpoint in APP/PS1 KI mice. bioRxiv. 2026. doi:10.64898/2026.09.29.755475.
BibTeX
@article{moallem2026-2631138c,
author = {Moallem, E. Z. and Bruntz, R. C. and Cox, M. F. and Bytyqi, L. and Roberts, T. K. and Patel, S. P. and Macheda, T. and Roberts, K. N. and others},
title = {{Closed-head injury produces a delayed, region-specific defect in glucose-carbon routing at the pyruvate branchpoint in APP/PS1 KI mice}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.09.29.755475},
url = {https://doi.org/10.64898/2026.09.29.755475}
}
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Key findings
- Traumatic brain injury (TBI) is a risk factor for Alzheimer’s disease (AD), and both conditions are associated with impaired glucose metabolism and mitochondrial dysfunction.
- These findings suggest that in APP/PS1 KI mice, chronic closed-head injury produced a delayed shift in glucose-derived carbon labeling centered on glycolytic and pyruvate/lactate nodes, with loss of hippocampal precursor-product coupling but without broad reduction of first-turn TCA-linked labeling.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on 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 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| 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 | Laboratory or animal study (title names “app/ps1”) — scores zero |
| 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 | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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