Epigenetic Alterations Associated with Alzheimer's Disease Progression

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@article{1720207,
      author = {Abolaji Tawakalitu Durodoye},
      title = {Epigenetic Alterations Associated with Alzheimer's Disease Progression},
      journal = {Iconic Research And Engineering Journals},
      year = {2026},
      volume = {10},
      number = {1},
      pages = {3827-3908},
      issn = {2456-8880},
      url = {https://www.irejournals.com/formatedpaper/1720207.pdf},
      abstract = {Alzheimer’s disease is a progressive neurodegenerative disorder characterised by cognitive decline, memory impairment, loss of functional independence, and extensive molecular and cellular abnormalities within the brain. Although genetic factors contribute substantially to disease susceptibility, inherited variation alone does not fully explain the heterogeneous onset, severity, progression, or clinical presentation of Alzheimer’s disease. Increasing evidence indicates that epigenetic mechanisms may mediate interactions among ageing, genetic susceptibility, environmental exposure, cellular stress, inflammation, and neurodegenerative processes.
Aim -This study aims to investigate epigenetic alterations associated with Alzheimer’s disease progression and to determine their potential relevance to disease mechanisms, biomarker development, prognosis, and therapeutic targeting.
Methods - For methodological demonstration, a deterministic synthetic cohort of 480 observations was generated (160 cognitively normal, 160 mild cognitive impairment and 160 Alzheimer’s disease). Variables represented demographic, cognitive, APOE, methylation, non-coding RNA, chromatin-accessibility, transcriptomic and epigenetic-age measures. Group comparisons, linear models, correlations and a 10-fold cross-validated logistic model were applied. The values are simulated and cannot establish clinical or biological effects.
In the simulated cohort, mean age, APOE ε4 frequency, Braak stage and cognitive impairment increased across diagnostic groups by construction. Synthetic methylation values at ANK1, BIN1, RHBDF2, HOXA3 and MCF2L increased with diagnostic stage. A multivariable model combining demographic and simulated molecular features yielded a 10-fold cross-validated AUC of 0.917. These estimates demonstrate the proposed analysis and reporting workflow only; they are not empirical Alzheimer’s disease findings.
Conclusion
The synthetic analysis shows that the proposed workflow can generate internally consistent tables, figures and model-performance estimates. It does not validate an epigenetic biomarker or support causal, diagnostic, prognostic or therapeutic claims. A submission-ready thesis requires verified participant or public-cohort data, documented provenance, ethics/data-use approval, reproducible analysis code and external validation.},
      keywords = {Alzheimer’s Disease, Epigenetics, DNA Methylation, Histone Modification, Chromatin Accessibility, Non-Coding RNA, Neurodegeneration, Cognitive Decline.},
      month = {July},
      doi = {https://doi.org/10.64388/IREV10I1-1720207}
  }