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Lookup NU author(s): Dr Connor Richardson
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 by the authors.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.
Author(s): Vazquez-Villasenor I, Benson B, Richardson CD, Waller R, Castelli LM, Simpson JE, Matthews FE, Brayne C, Wharton SB
Publication type: Article
Publication status: Published
Journal: International Journal of Molecular Sciences
Year: 2026
Volume: 27
Issue: 15
Online publication date: 03/08/2026
Acceptance date: 30/07/2026
Date deposited: 25/08/2026
ISSN (print): 1661-6596
ISSN (electronic): 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
URL: https://doi.org/10.3390/ijms27156964
DOI: 10.3390/ijms27156964
Data Access 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.
PubMed id: 42589618
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