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Spatiotemporal transcriptomic profiling reveals upregulation of glycolysis pathway genes before overt tauopathy in the PS19 mouse model
Shuai Wang, Moorthi Ponnusamy, Om Patel, Mitchell T. Hansen, Lisa A. Collier, Shane Collier, Gopal Thinakaran. Experimental & Molecular Medicine, 2026-02-13
Topic: Brain proteins, microglia and lab models
The abnormal accumulation of hyperphosphorylated tau in neurofibrillary tangles is a hallmark of neurodegenerative diseases, such as Alzheimer's disease (AD) and frontotemporal dementia. In AD, tangle pathology characteristically develops in brain regions with heightened vulnerability, such as the entorhinal cortex and hippocampus. Emerging evidence implicates mitochondrial dysfunction and metabolic disturbances in AD progression, yet the relationship between regional vulnerability and pretangle tau-driven transcriptomic changes remains unclear. Here, to address this critical gap, we utilized the tau P301S transgenic mouse model (PS19 line), which develops tau inclusions. Using spatial transcriptomic profiling across the hippocampal and cortical regions at selected disease stages, we captured spatiotemporal transcriptional responses to tauopathy. Our findings reveal that disease-associated microglia and astrocyte phenotypes emerge concurrently with phosphorylated tau accumulation across multiple brain regions. Intriguingly, the expression of Pgk1, a hub gene of the glycolytic pathway, was upregulated along with other metabolic pathway genes in the CA3 region at 2 months of age, preceding the onset of detectable tau tangle pathology, and correlated with tangle severity, suggesting early metabolic dysregulation in vulnerable regions. Further analysis of differentially expressed genes uncovered region-specific and temporally dynamic transcriptional patterns in the cortex and hippocampus. Early saturable alterations in ATP metabolic processes, glycolysis and oxidative phosphorylation appeared in the hippocampus at 2 months of age, with delayed engagement in the cortical regions. These results underscore the contributions of metabolic stress and glial activation to tauopathy and regional vulnerability, highlighting spatial transcriptomics as a powerful tool for uncovering region-specific molecular insights into disease mechanisms.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Wang, S., Ponnusamy, M., Patel, O., Hansen, M. T., Collier, L. A., Collier, S., et al. (2026). Spatiotemporal transcriptomic profiling reveals upregulation of glycolysis pathway genes before overt tauopathy in the PS19 mouse model. Experimental & Molecular Medicine. https://doi.org/10.1038/s12276-026-01652-z
Vancouver
Wang S, Ponnusamy M, Patel O, Hansen MT, Collier LA, Collier S, et al. Spatiotemporal transcriptomic profiling reveals upregulation of glycolysis pathway genes before overt tauopathy in the PS19 mouse model. Experimental & Molecular Medicine. 2026. doi:10.1038/s12276-026-01652-z. PMID: 41688738.
BibTeX
@article{wang2026-41688738,
author = {Wang, Shuai and Ponnusamy, Moorthi and Patel, Om and Hansen, Mitchell T. and Collier, Lisa A. and Collier, Shane and Thinakaran, Gopal},
title = {{Spatiotemporal transcriptomic profiling reveals upregulation of glycolysis pathway genes before overt tauopathy in the PS19 mouse model}},
journal = {Experimental \& Molecular Medicine},
year = {2026},
doi = {10.1038/s12276-026-01652-z},
pmid = {41688738},
url = {https://doi.org/10.1038/s12276-026-01652-z}
}
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.
Key findings
- Our findings reveal that disease-associated microglia and astrocyte phenotypes emerge concurrently with phosphorylated tau accumulation across multiple brain regions.
- These results underscore the contributions of metabolic stress and glial activation to tauopathy and regional vulnerability, highlighting spatial transcriptomics as a powerful tool for uncovering region-specific molecular insights into disease mechanisms.
Why it matters
In the PS19 tau mouse model, spatial transcriptomics showed that glycolysis pathway genes, including Pgk1, were upregulated in the CA3 region at 2 months of age, before detectable tau tangles. The findings point to early metabolic dysregulation and glial activation in vulnerable brain regions, based on animal work.
Study details
- Evidence strengthLow
How this study scored 44/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Experimental & Molecular Medicine) |
| Journal's citation record | 2 / 4 | Experimental & Molecular Medicine: journal h-index 181 (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 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 7 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 5 / 6 | Cited 25.0× 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 | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Gopal Thinakaran: h-index 67 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of South Florida: institution h-index 806 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41688738) |
| Free to read | 2 / 2 | Free to read |
| Total | 44 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s12276-026-01652-z
- PubMed: 41688738
- Original source →
- Free full text: Experimental & Molecular Medicine →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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