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Association between APOE genotype and microglial cell morphology.

Courtney M Kloske1, Mary D Gearon2, Erica M Weekman1

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|April 22, 2023
PubMed
Summary

Apolipoprotein E (ApoE) isoforms influence Alzheimer's disease (AD) risk. This study found ApoE isoforms impact microglial activation and morphology, suggesting their importance in AD neuroinflammation.

Keywords:
Alzheimer diseaseApoEMicrogliaNeuropathology

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Area of Science:

  • Neuroscience
  • Genetics
  • Immunology

Background:

  • Apolipoprotein E (ApoE) is a major genetic risk factor for late-onset Alzheimer's disease (AD).
  • The E4 isoform (ApoE4) increases AD risk compared to the E3 isoform (ApoE3).
  • ApoE's role in brain neuroinflammation, particularly its impact on microglia, is not fully understood.

Purpose of the Study:

  • To investigate the impact of different Apolipoprotein E (ApoE) isoforms on microglial morphology and activation.
  • To determine if ApoE isoforms influence neuroinflammatory responses in Alzheimer's disease (AD).

Main Methods:

  • Immunohistochemistry was used to analyze microglial markers.
  • Digital image analysis quantified microglial morphology and activation states.
  • Ionized calcium-binding adaptor molecule 1 (Iba1) immunoreactivity was assessed in brain regions of AD participants and controls.

Main Results:

  • Microglial activation was elevated in dementia participants compared to controls in the hippocampus and superior and middle temporal gyrus (SMTG).
  • Specific microglial morphologies, such as ramified microglia, were reduced in the dementia group.
  • ApoE isoforms were associated with distinct changes in microglial morphology, with rod microglia showing differential distribution in E4 carriers.

Conclusions:

  • Apolipoprotein E (ApoE) isoforms are associated with altered microglial activation and morphology in Alzheimer's disease (AD).
  • These findings underscore the significance of considering ApoE isoforms in understanding AD neuropathology and neuroinflammation.
  • Microglial responses vary depending on both dementia status and ApoE genotype.