Epigenomic subtypes of late-onset Alzheimer’s disease reveal distinct microglial signatures - Summary - MDSpire

Epigenomic subtypes of late-onset Alzheimer’s disease reveal distinct microglial signatures

  • By

  • Valentin T. Laroche

  • Rachel Cavill

  • Morteza Kouhsar

  • Joshua Müller

  • Rick A. Reijnders

  • Joshua Harvey

  • Adam R. Smith

  • Jennifer Imm

  • Jarno Koetsier

  • Luke Weymouth

  • Lachlan MacBean

  • Giulia Pegoraro

  • Lars Eijssen

  • Byron Creese

  • Gunter Kenis

  • Betty M. Tijms

  • Daniel van den Hove

  • Katie Lunnon

  • Ehsan Pishva

  • February 24, 2026

  • 0 min

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Objective:

To identify epigenomic-based subtypes of late-onset Alzheimer’s disease (LOAD) using genome-wide DNA methylation data, highlighting the significance of these subtypes in understanding disease heterogeneity.

Key Findings:
  • Identified distinct molecular subtypes of LOAD based on DNA methylation patterns, which may inform targeted therapeutic strategies.
  • Subtypes correlated with immune activation, protein metabolism, and organic acid metabolic processes, suggesting diverse underlying mechanisms.
  • Transcriptomic correlates for each subtype were identified using bulk and single-nucleus RNA sequencing data, enhancing our understanding of LOAD's molecular landscape.
Interpretation:

The study highlights the role of epigenetic modifications in understanding the heterogeneity of LOAD, suggesting that distinct DNAm subgroups may exist within AD, which could guide future research directions.

Limitations:
  • The study is limited to postmortem brain samples, which may not fully represent the disease in living patients; future studies should consider longitudinal designs.
  • Potential confounding factors related to environmental and lifestyle influences on DNAm were not fully explored, indicating a need for comprehensive assessments in future research.
Conclusion:

The findings contribute to a deeper understanding of LOAD's molecular landscape and may inform future therapeutic strategies targeting specific subtypes, emphasizing the importance of personalized medicine in AD treatment.

Original Source(s)

Epigenomic subtypes of late-onset Alzheimer’s disease reveal distinct microglial signatures

  • by Valentin T. Laroche, Rachel Cavill, Morteza Kouhsar, Joshua Müller, Rick A. Reijnders, Joshua Harvey, Adam R. Smith, Jennifer Imm, Jarno Koetsier, Luke Weymouth, Lachlan MacBean, Giulia Pegoraro, Lars Eijssen, Byron Creese, Gunter Kenis, Betty M. Tijms, Daniel van den Hove, Katie Lunnon, Ehsan Pishva

  • February 24, 2026

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