Postmortem Interval Leads to Loss of Disease-Specific Signatures in Brain Tissue
Open accessAbstract
Human brain banks are essential for studying a wide variety of neurological and neurodegenerative diseases, yet the variability in postmortem interval (PMI)—the time from death to tissue preservation—poses significant challenges due to rapid cellular decomposition, protein alterations, and RNA degradation. Furthermore, the postmortem transcriptomic alterations occurring within distinct cell types are poorly understood. In this study, we analyzed the effect of a 3 h postmortem interval on single-nucleus RNA signatures in the brains of wild-type (WT) and PS19 mice, a common model of tauopathy. We observed that basic quality control metrics (such as the number of genes and reads per cell), total nuclei counts, and RNA integrity number (RIN e ) remained consistent across all samples, regardless of PMI or genotype. However, a 3 h PMI diminished the number of genes differentially expressed between PS19 and WT mice, suggesting an impact of delayed processing on the detection of disease-specific transcriptomic signatures. When directly comparing 3 h PMI versus freshly harvested 0 h mouse brains, we identified genes upregulated in neurons and interneurons involved in DNA repair, immune response, and stress pathways. Furthermore, genes that were altered in non-neuronal cell types at 3 versus 0 h PMI were associated with cell–cell adhesion processes. These findings highlight the effects of PMI on single-nucleus transcriptional changes that may dampen the true changes in cellular states in banked brain tissues.
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A 3-hour PMI in PS19 at 4°C before tissue processing substantially reduces the disease-associated transcriptional signature in neurons, despite minimal effects on RNA Integrity Number (RIN).
“A 3‐hour PMI in PS19 at 4°C before tissue processing substantially reduces the disease‐associated transcriptional signature in neurons, despite minimal effects on RNA Integrity Number (RIN). 75”
From Unique transcriptomic alterations in 5XFAD;PS19 mouse model identify glial lipid dysregulation and coordinated microglial–oligodendrocyte responses (2026) · cites this paper as [75]
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- Authors
- Olney, K. C., Gibson, K. A., Cadiz, M. P., Rahimzadeh, N., Swarup, V., & Fryer, J. D.
- Affiliations
- Translational Genomics Research Institute (US)
- Mayo Clinic (US)
- University of California, Irvine (US)
- Corresponding author
- Olney, Kimberly C.
- Fryer, John D.
- Venue
- eneuro
- Publisher
- Society for Neuroscience
- Published
- 2025-02-27
- Volume
- 12
- Issue
- 3
- Pages
- ENEURO.0505-24.2025
- ISSN
- 2373-2822 (ISSN-L)
- PMC
- PMC11913402
- OpenAlex
- W4408017396
- Cited by
- 22
- References
- 24
- Citations by year
- 2026: 18 · 2025: 4
- FWCI
- 6.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- eNeuro (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institute of General Medical Sciences (T32GM136624)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
- Keywords
- postmortem interval, brain tissue preservation, single-nucleus RNA sequencing, tauopathy, PS19 mice, RNA integrity, DNA repair, immune response, cell-cell adhesion, neurodegenerative disease models
- MeSH terms
- Animals, Brain, Disease Models, Animal, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Postmortem Changes, Time Factors, Tauopathies, Mice, Transcriptome
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