Alzheimer’s disease (AD) is one of the most pressing public health challenges in ageing populations, yet its causal mechanisms remain incompletely understood. Increasing evidence suggests that cellular senescence-a hallmark of biological ageing-may contribute to neurodegenerative processes by promoting inflammation, mitochondrial dysfunction, and glial cell impairment. However, existing studies are largely observational, and causal relationships between senescence markers and AD have not been systematically validated in large-scale human cohorts.
This student-led project aims to investigate whether molecular and genetic signatures of cellular senescence are causally associated with the risk of Alzheimer’s disease. Using data from the UK Biobank, combined with publicly available summary statistics from IGAP and ADNI, the study will apply a Mendelian Randomization (MR) framework to infer causality between genetic proxies of senescence (e.g., telomere length, p16, IL-6, TNF-!) and AD susceptibility. Additional analyses will explore potential mediating pathways and molecular mechanisms through transcriptomic and proteomic validation.
The findings are expected to clarify the causal role of senescence in AD pathogenesis and identify potential biomarkers or therapeutic targets for early intervention. This project forms part of the applicant’s postgraduate thesis, conducted under academic supervision, and is entirely non-commercial.