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Sex-specific factors and APOEε4 genotype alter functional connectivity at middle age.

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Basic Science and Pathogenesis.

Bonnie H Lee1, Andrew J McGovern2, Stephanie E Lieblich3

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Summary
This summary is machine-generated.

Primiparity benefits wildtype rats but harms neural networks in APOEε4 rats, impacting cognitive strategies. Understanding within-sex factors is crucial for Alzheimer's disease (AD) research.

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Area of Science:

  • Neuroscience
  • Genetics
  • Aging Research

Background:

  • Females face higher Alzheimer's disease (AD) risk and cognitive decline.
  • APOEε4 allele exacerbates AD risk and burden in females.
  • Parity (pregnancy/parenthood) influences brain aging and AD risk in females.

Purpose of the Study:

  • Investigate the effects of parity and humanized APOEε4 (hAPOEε4) genotype on brain activation and connectivity.
  • Explore how these factors influence cognitive function in middle-aged female rats.

Main Methods:

  • Compared nulliparous and primiparous wildtype and hAPOEε4 rats.
  • Assessed spatial working memory performance.
  • Examined neural activation and functional connectivity using zif268 in 19 brain regions post-memory retrieval.

Main Results:

  • Primiparity enhanced neural network efficiency in wildtype rats.
  • Primiparity fragmented neural networks and reduced activation in hAPOEε4 rats.
  • Specific brain region activation predicted cognitive strategy use, dependent on hAPOEε4 genotype.

Conclusions:

  • Parity and hAPOEε4 genotype distinctly alter neural network organization and regional importance for cognition.
  • Within-sex factors are critical for understanding AD risk and brain health outcomes.