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Basic Science and Pathogenesis.

Shiva Kazempour Dehkordi1, Habil Zare2, Miranda E Orr3

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Summary
This summary is machine-generated.

Cellular senescence, or neurescence, is linked to Alzheimer's disease. The thalamus shows the highest proportion of senescent neurons, highlighting its importance in neurodegenerative disease research.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Genomics

Background:

  • Cellular senescence is implicated in neurodegenerative diseases like Alzheimer's.
  • Neurescence (senescent neurons) was previously identified in the prefrontal cortex.
  • The prevalence of neurescence in other brain regions was unknown.

Purpose of the Study:

  • To identify senescent cell types across six brain regions.
  • To investigate the role of senescence in Alzheimer's disease pathology.
  • To determine the distribution of senescent neurons in the human brain.

Main Methods:

  • Analyzed single nucleus RNA-Seq data from 48 postmortem human brains.
  • Utilized an eigengene-based approach to assess senescence pathways (SenMayo, CSP, SIP).
  • Classified cells as senescent if three key eigengenes exceeded mean + 3 standard deviations.

Main Results:

  • Excitatory neurons were the only cell type consistently associated with senescence across all analyzed regions.
  • Senescence signatures were robust and shared molecular features across different gene panels.
  • The thalamus exhibited the highest neurescence ratio (9%), significantly higher than other regions (1%-4%).

Conclusions:

  • The thalamus is a critical region for studying neurescence due to its high senescent neuron ratio.
  • This study is the first to identify excitatory and inhibitory neurons as key senescent cell types in the thalamus.
  • Findings contribute to understanding the role of cellular senescence in brain aging and neurodegeneration.