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Do senescent cells play a role in Alzheimer’s disease?
Author(s) -
Walker Lauren,
Jacobs Eleanor,
McAleese Kirsty E.,
Johnson Mary,
Attems Johannes
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.043820
Subject(s) - tauopathy , senescence , phenotype , ageing , alzheimer's disease , senile plaques , astrocyte , pathology , cortex (anatomy) , disease , neuroscience , biology , medicine , neurodegeneration , microbiology and biotechnology , central nervous system , genetics , gene
Background Cellular senescence, the irreversible arrest of the cell cycle, is a common occurrence in ageing. Astrocytes have been shown to demonstrate a senescent phenotype, which is increased in ageing, and in Alzheimer’s disease (AD) (as evidenced by p16 INK4a expression). Recently, a causal link was established between p16 INK4a expression and hyperphosphorylated tau (HPT) pathology in the MAPT P301S PS19 mouse model of tauopathy, where treatment with a senolytic agent removed senescent p16 INK4a positive astrocytes, prevented aggregation of HPT, and preserved cognitive function, suggesting senescent astrocytes may play a role in HPT deposition observed in AD. However, data in human post‐mortem tissue from AD cases (inclusive of Aβ pathology) is lacking. Method Frontal cortex (BA9) from 10 AD and 10 control cases were double immunolabelled for GFAP and p16 INK4a . A mean number of p16 INK4a positive astrocytes (identified by the presence of co‐localisations) was determined at 6 regions of interest across each section. HPT and Aβ were quantified by percentage area of immunopositivity in the same region. Result AD cases had significantly more p16 INK4a positive astrocytes compared to controls (p<0.05). We observed a positive association between number of p16 INK4a positive astrocytes and HPT load in AD cases (p<0.05). No association was observed between the mean number of p16 INK4a positive astrocytes and Aβ load. Conclusion We found a positive association was found between p16 INK4a positive astrocytes and HPT. This area of research warrants further investigation to determine whether the development of senolytic therapies are a viable option for the treatment of AD and other tauopathies.