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A significant amount of neuroscience research relies on human post-mortem brain tissue, the quality of which deteriorates after death. A recently published Nature Communications study, led by scientists from ÌìÃÀ´«Ã½ and McGill University, suggested that while time is an important factor, temperature may play an even greater role in brain tissue preservation than previously thought.

Better quality brain tissue data could accelerate the development of treatments for neurodegenerative diseases and inform best practices for how brain banks collect and preserve tissue worldwide. 

The challenges of brain tissue collection  

Gene expression research is the study of which genes are active in each tissue and to what degree. In brain research, it has helped identify biological markers for Alzheimer’s disease, Parkinson’s disease, certain cancers, and psychiatric conditions such as schizophrenia.¹ 

The time between death and tissue collection, known as the postmortem interval (PMI), is considered to be a key factor in determining the quality of brain tissue samples.² Previous research confirmed that within just a few hours of death, genes associated with neuronal activity begin to shut down, while immune cells – microglia and astrocytes – respond to the damage and begin clearing dying cells.  

The longer the tissue is left before collection, the more its genetic profile diverges from what it looked like in a living brain.³ 

Brain, time, and temperature – the key findings 

The  study compared gene expression in brain tissue extracted immediately from brains during surgery (< 0 hours) and brain tissue with short (~6 hours) and long (~36 hours) post-mortem intervals (PMIs). Researchers confirmed that even a 6-hour postmortem interval caused significant changes in gene activity compared to freshly extracted tissue. The genes driving these deviations were named Brain Artifact Genes (BAGs).  

“This work has also shown that the temperature at which the brain is kept may have greater implications than the time before being used in post-mortem transcriptomics studies”, says Dr , Advanced Research Fellow in the Department of Brain Sciences at Imperial and a co-corresponding author. To separate the effects of time and temperature, the team stored fresh tissue at either room temperature (20°C) or in a fridge (4°C) for 6, 24, and 36 hours. Tissue kept at 4°C for 6 hours showed no changes, while just 6 hours at room temperature was enough to trigger them.  

This work has also shown that the temperature at which the brain is kept may have greater implications than the time before being used in post-mortem transcriptomics studies. Dr Johanna Jackson Advanced Research Fellow in the Department of Brain Sciences

Researchers also proved that different brain cell types were affected at different times. After six hours at room temperature, glutamatergic neurons, responsible for memory and learning, were the first to show damage, followed by GABAergic neurons, which regulate mood, sleep and anxiety. At 24 hours, oligodendrocytes, which allow signals to travel efficiently, became the most affected, followed by microglia, the brain’s immune cells.  

An open-source AI resource 

Until now, there was no tool available to systematically measure and account for these changes. Using deep learning, the team distilled the broader processing-response program into a compact, predictive signature called Time and Temperature Response genes Underlying Transcriptional Heterogeneity (TTRUTH).  

The model assigns a continuous score to individual autopsy samples, estimating the extent to which time and temperature have affected their gene activity data. The tool is freely available to the global research community at , allowing brain banks worldwide to better standardise datasets and enhance data interpretation. 

"This is an excellent online resource so anyone can upload datasets to this user-friendly open website to identify brain-relevant transcripts susceptible to processing artifacts," explains Dr Jo Anne Stratton, from McGill University, co-corresponding author. Brain autopsies are notoriously time-consuming and unpredictable, and RNA, which degrades rapidly after death, makes interpreting data on gene activity in brain tissue) particularly challenging. "We hope this resource will help, even just a little, to make better sense of the vast number, and ever-growing, brain omics datasets out there," adds Dr Stratton.  

The future of brain banking 

Globally, tens of millions of people live with neurodegenerative conditions, including dementia, Parkinson's disease, and MS 5. These figures likely underestimate the true scale, particularly in lower-income countries, where limited specialist services, stigma, and inadequate research infrastructure mean many cases go undetected.⁴ Understanding these diseases depends on access to high-quality, diverse human brain tissue, making the work of brain banks essential. 

“This study addresses an important source of potential bias in the study of post-mortem human tissues with the increasingly widely used single nuclear transcriptomic technologies,” explains Professor Paul Matthews, Edmond and Lily Safra Chair at the Department of Brain Sciences at Imperial and article co-author. In other words, what looks like a biological difference may simply be an artefact of how the tissue was handled after death. 

The researchers analysed tissue from McGill in Canada and post-mortem tissue from brain banks in the UK and the Netherlands. “What is exciting is that it suggests that the time- and temperature-dependent changes are consistent enough to allow them to be recognised and allowed for in interpretation of the data,” Professor Matthews adds.  

As Dr Jackson emphasises: “Whilst time and temperature are both important, this means that if the brain can be kept cool as soon as possible after death, the quality of the data may be improved. This has implications for post-mortem and brain banking services.”  

The UK maintains 10 brain bank centres holding samples from more than 10,000 donated brains⁵. The Multiple Sclerosis and Parkinson’s Tissue Bank at ÌìÃÀ´«Ã½ is one of the UK's most specialised, focusing on Parkinson's disease, Multiple System Atrophy, and MS. Unlike many banks that rely solely on post-mortem donations, it works closely with living donors who register their wish to donate during their lifetime, allowing researchers to track disease progression over time, and supplies tissue to scientists globally. Better quality data could accelerate the development of treatments for neurodegenerative diseases.  

More: 

• Yaqubi, M., Thomas, M., Talbot-Martin, J. et al. Characterising processing conditions that artifactually bias human brain tissue transcriptomes. Nat Commun 17, 2848 (2026).

 [1]  Zhang Z, et al., Front Neurosci. 2024 doi: 10.3389/fnins.2024.1358998; Forés-Martos J, et al.,  Cancers (Basel). 2021 doi: 10.3390/cancers13122990; Hatano M, et al.,  Neuropsychopharmacol Rep. 2025 doi: 10.1002/npr2.70053.

[2] Birdsill AC, et al., Cell Tissue Bank. 2011. doi: 10.1007/s10561-010-9210-8. 

[3] Dachet, F. et al., Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain. Sci Rep 11, 6078 (2021).

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