Early amyloid-induced changes in microglia gene expression in male APP/PS1 mice

Research output: Contribution to journalJournal articleResearchpeer-review

  • Takuya Oshima
  • Mandy S.J. Kater
  • Christiaan F.M. Huffels
  • Evelyn M. Wesseling
  • Jinte Middeldorp
  • Elly M. Hol
  • Mark H.G. Verheijen
  • August B. Smit
  • Boddeke, Erik
  • Bart J.L. Eggen

Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia, characterized by deposition of extracellular amyloid-beta (Aβ) aggregates and intraneuronal hyperphosphorylated Tau. Many AD risk genes, identified in genome-wide association studies (GWAS), are expressed in microglia, the innate immune cells of the central nervous system. Specific subtypes of microglia emerged in relation to AD pathology, such as disease-associated microglia (DAMs), which increased in number with age in amyloid mouse models and in human AD cases. However, the initial transcriptional changes in these microglia in response to amyloid are still unknown. Here, to determine early changes in microglia gene expression, hippocampal microglia from male APPswe/PS1dE9 (APP/PS1) mice and wild-type littermates were isolated and analyzed by RNA sequencing (RNA-seq). By bulk RNA-seq, transcriptomic changes were detected in hippocampal microglia from 6-months-old APP/PS1 mice. By performing single-cell RNA-seq of CD11c-positive and negative microglia from 6-months-old APP/PS1 mice and analysis of the transcriptional trajectory from homeostatic to CD11c-positive microglia, we identified a set of genes that potentially reflect the initial response of microglia to Aβ.

Original languageEnglish
Article numbere25295
JournalJournal of Neuroscience Research
Volume102
Issue number3
Number of pages14
ISSN0360-4012
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2024 Wiley Periodicals LLC.

    Research areas

  • Alzheimer's disease, amyloid, microglia, neuroinflammation, RNA-seq, RRID:AB_11203704, RRID:AB_2056966, RRID:AB_2336180, RRID:AB_2340593, RRID:AB_2563061, RRID:AB_2629529, RRID:AB_313038, RRID:AB_313776, RRID:AB_465051, RRID:AB_467134, RRID:AB_839504

ID: 387266660