Senescence Markers and Associated Transcriptomic Changes Are Expressed at Early Stages of Alzheimer's Neuropathology but Are Not Independently Related to Dementia.

Overview

1. Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK
2. Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
3. Institute for Clinical and Applied Research, University of Hull, Hull HU6 7RX, UK
4. Cambridge Public Health, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SP, UK

Abstract

Cellular senescence may affect the post-mitotic cells of the brain. We examined the expression of senescence markers, including p16, p21, γH2Ax and H3K9me3, in the frontal cortex of brain donations from the Cognitive Function and Ageing Study to assess their relationship to Alzheimer’s disease neuropathological change (ADNC) and dementia. p21, γH2Ax and H3K9me3 were expressed in pyramidal neurons and glia, whilst p16 was confined to glial cells. p21 and γH2Ax were correlated in neurons, and with p16 in glia. They did not increase with ADNC, tending to be higher at early Braak neurofibrillary tangle stages. Transcriptomic profiling of pyramidal neuron-enriched samples at low Braak stages showed that higher neuronal p21 expression was associated with altered pathways for neuronal function, neurodegeneration, protein homeostasis, mitochondrial dysfunction and synaptic signalling. In conclusion, the different expression profile of senescence markers in neurons and glia suggest possible differences in senescence-related mechanisms. Expression at lower ADNC stages suggests senescence may be important at earlier stages of Alzheimer’s pathogenesis, whilst transcriptomic changes suggest an impact on neuronal function. The lack of association of senescence markers with dementia status indicates that more work is needed to determine the value of senescence as a therapeutic target for dementia.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

• geo:GSE310124, at NCBI GEO; found in the text, “2.4. Gene Expression Changes Associated with…”

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to ethical restrictions of CFAS.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 7 keywords, 14 MeSH terms, 3 funders, 53 references.

Cite

This paper

Vazquez-Villaseñor, I., Benson, B., Richardson, C. D., Waller, R., Castelli, L. M., Simpson, J. E., Matthews, F. E., Brayne, C., & Wharton, S. B. (2026). Senescence Markers and Associated Transcriptomic Changes Are Expressed at Early Stages of Alzheimer's Neuropathology but Are Not Independently Related to Dementia. International journal of molecular sciences, 27(15), 6964. https://doi.org/10.3390/ijms27156964

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1038/s41588-026-02722-8 [code]

A multiancestry polygenic risk score for Alzheimer's disease is associated with cognitive decline and neuropathological hallmarks in diverse populations.

Journal: Nature genetics

In common: histology / microscopy, Alzheimer's / dementia, genetics / omics, 1 other category, 3 references

[2] doi:10.1007/s00401-026-03039-w [code]

Correlative ultrastructural mapping of Lewy pathology reveals regional diversity in Parkinson's and dementia with Lewy bodies.

Journal: Acta neuropathologica

In common: histology / microscopy, Alzheimer's / dementia, cellular / molecular, 3 references

[3] doi:10.1038/s41593-026-02320-1 [code]

The mitochondrial unfolded protein response in human microglia disrupts neuronal-glial communication and promotes senescence.

Journal: Nature neuroscience

In common: cellular / molecular, 3 references

[4] doi:10.1016/j.xcrm.2026.102968 [code]

Corpora amylacea profiling reveals disease stage and brain region-specific alterations in glycogen metabolism in Alzheimer's disease patient brains.

Journal: Cell reports. Medicine

In common: histology / microscopy, Alzheimer's / dementia, 3 references

[5] doi:10.1002/alz.71649 [code]

Postmortem brain MRI reveals differential associations of subcortical and limbic volumes with cortical thinning and neurodegenerative pathologies.

Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association

In common: histology / microscopy, Alzheimer's / dementia, cellular / molecular, 2 references

[6] doi:10.1093/jnen/nlaf152 [code]

Clinical and pathologic correlations of machine learning quantification of Aβ deposits across 3 brain regions of decedents with Alzheimer disease.

Journal: Journal of neuropathology and experimental neurology

In common: Alzheimer's / dementia, 3 references

[7] doi:10.3390/cimb48070691

Astrocyte Subtype-Specific Expression of the Sodium-Coupled Citrate Transporter <i>SLC13A5</i> and Citrate Metabolism Genes Across Alzheimer's Disease Pseudoprogression: A Single-Nucleus RNA Sequencing Analysis of the Human Middle Temporal Gyrus.

Journal: Current issues in molecular biology

In common: Alzheimer's / dementia, genetics / omics, cellular / molecular, 3 references

[8] doi:10.1002/cns.71021

Multilayer Proteome and Metabolome-Based Validation Uncovers Combined Regulatory Roles and Predictive Values of 6 RNA Modifications and Cellular Senescence in Alzheimer's Disease.

Journal: CNS neuroscience & therapeutics

In common: Alzheimer's / dementia, genetics / omics, cellular / molecular, 2 references

[9] doi:10.1371/journal.pgen.1012170 [code]

Genome wide association study meta-analysis of neuropathologic lesions of Alzheimer's disease and related dementias in a multi-site autopsy cohort.

Journal: PLoS genetics

In common: histology / microscopy, Alzheimer's / dementia, genetics / omics, 2 references

[10] doi:10.1038/s41514-026-00391-9 [code]

Region-specific transcriptional signatures of brain aging in the absence of neuropathology at the single-cell level.

Journal: npj aging

In common: histology / microscopy, genetics / omics, cellular / molecular, 2 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.