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Basic Science and Pathogenesis.

Jaclyn Iannucci1, Reagan Dominy1, Saloni Tipnis1

  • 1Texas A&M Health Science Center, Bryan, TX, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
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Summary

Traumatic brain injury (TBI) exacerbates Alzheimer's disease (AD) risk. Targeting B cells after TBI shows therapeutic potential, with sex-specific behavioral improvements observed in mice.

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Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Traumatic brain injury (TBI) is a significant risk factor for Alzheimer's disease (AD) and related dementias (ADRDs).
  • Inflammation is a key factor in both TBI and AD pathogenesis.
  • Previous research indicates B cells play a role in TBI outcomes.

Purpose of the Study:

  • To investigate if exacerbation of AD-like pathology and cognitive decline after TBI is linked to B cell expansion.
  • To determine if targeting B cells therapeutically can improve outcomes post-TBI.
  • To explore sex-based differences in TBI and AD pathology and treatment response.

Main Methods:

  • Male and female 5xFAD mice underwent fluid percussion injury (FPI) or sham surgery.
  • B cell depletion therapy was administered post-FPI.
  • Neurobehavioral tests (burrowing, social interaction, EPM, Y-maze, PST) and neuropathological assessments were performed.

Main Results:

  • Significant sex differences were observed in behavioral responses to FPI and B cell depletion.
  • B cell depletion improved anxiety behaviors in male mice but not females.
  • Improvements in Y-maze performance after B cell depletion were more pronounced in female mice.

Conclusions:

  • Targeting B cells presents a potential therapeutic strategy for TBI and its link to AD.
  • Investigating biological sex is crucial for understanding TBI and AD.
  • Sex-specific responses highlight the need for tailored therapeutic approaches.