Sex- and region-specific cortical and hippocampal whole genome transcriptome profiles from control and APP/PS1 Alzheimer's disease mice

PLoS One. 2024 Feb 7;19(2):e0296959. doi: 10.1371/journal.pone.0296959. eCollection 2024.

Abstract

A variety of Alzheimer's disease (AD) mouse models has been established and characterized within the last decades. To get an integrative view of the sophisticated etiopathogenesis of AD, whole genome transcriptome studies turned out to be indispensable. Here we carried out microarray data collection based on RNA extracted from the retrosplenial cortex and hippocampus of age-matched, eight months old male and female APP/PS1 AD mice and control animals to perform sex- and brain region specific analysis of transcriptome profiles. The results of our studies reveal novel, detailed insight into differentially expressed signature genes and related fold changes in the individual APP/PS1 subgroups. Gene ontology and Venn analysis unmasked that intersectional, upregulated genes were predominantly involved in, e.g., activation of microglial, astrocytic and neutrophilic cells, innate immune response/immune effector response, neuroinflammation, phagosome/proteasome activation, and synaptic transmission. The number of (intersectional) downregulated genes was substantially less in the different subgroups and related GO categories included, e.g., the synaptic vesicle docking/fusion machinery, synaptic transmission, rRNA processing, ubiquitination, proteasome degradation, histone modification and cellular senescence. Importantly, this is the first study to systematically unravel sex- and brain region-specific transcriptome fingerprints/signature genes in APP/PS1 mice. The latter will be of central relevance in future preclinical and clinical AD related studies, biomarker characterization and personalized medicinal approaches.

MeSH terms

  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Disease Models, Animal
  • Female
  • Hippocampus / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism
  • Transcriptome

Substances

  • Proteasome Endopeptidase Complex
  • Amyloid beta-Protein Precursor
  • Presenilin-1
  • Amyloid beta-Peptides

Grants and funding

The study was internally funded by the Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM, Bonn, Germany). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript