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Basic Science and Pathogenesis.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2025
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Basic Science and Pathogenesis.

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Basic Science and Pathogenesis.

Klarissa Leduc1

  • 1Université de Montréal, Montréal, QC, Canada.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Alzheimer's disease (AD) pathology involves amyloid-beta oligomers (Aßo) impacting memory centers. This study reveals Aßo-induced gene changes in mouse brain cells, offering therapeutic targets for neurodegeneration.

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Area of Science:

  • Neuroscience
  • Genomics
  • Epigenetics

Background:

  • Alzheimer's disease (AD) is a leading cause of dementia, characterized by amyloid-beta oligomer (Aßo) aggregation.
  • Aßo accumulation precedes clinical AD symptoms by 10-15 years and is linked to hippocampal synaptic loss and neuronal death.

Purpose of the Study:

  • To investigate the specific gene expression and DNA accessibility changes induced by Aßo in various brain cell types.
  • To understand the impact of Aßo on cellular function during aging in the context of AD.

Main Methods:

  • Daily hippocampal injection of Aßo into mice (6, 12, and 18 months old) for 5 days.
  • Isolation of hippocampal single-cell nuclei for integrated transcriptomic and epigenetic analysis (snRNA-seq + ATAC-seq).
  • Analysis focused on neurons, astrocytes, oligodendrocytes, pericytes, endothelial cells, and microglia.

Main Results:

  • Identification of cell-type-specific gene expression alterations caused by Aßo.
  • Mapping of Aßo-induced changes in DNA accessibility sites across different brain cell populations.
  • Insights into the molecular mechanisms underlying Aßo-mediated neurodegeneration during aging.

Conclusions:

  • Understanding Aß pathology at a cellular level is crucial for developing early therapeutic interventions.
  • Targeting Aß-induced molecular changes may prevent irreversible brain damage and preserve cognitive function.
  • This research could lead to novel strategies for managing AD and improving patient quality of life.