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NIH Research Festival

September 23 – 25, 2024

Exploring amyloid beta-induced NF-κB dynamics in aging and Alzheimer’s Disease in vitro

Authors

  • P Songkiatisak
  • M Aqdas
  • SMT Rahman
  • K Oh
  • MH Sung

Abstract

Alzheimer’s Disease (AD) is characterized by the presence of extracellular amyloid beta (Aβ) and intracellular hyperphosphorylated tau (p-tau) proteins. Aβ plays a central role in AD progression due to its neurotoxic and inflammatory effects. Nuclear factor kappa B (NF-κB) is a well-known inflammatory transcription factor that contributes to neurodegeneration. Microglia, the brain-resident macrophages, are primarily responsible for protecting the brain from pathogens and clearing cellular debris, including Aβ. Activation of NF-κB signaling and the subsequent release of cytokines and chemokines from microglia can contribute to chronic inflammation in AD. Our previous in vitro findings indicated that most microglial cells formed cell clusters, referred to as “clustered microglia,” while a smaller subset exhibited high motility and smaller cell size, termed “free-roaming microglia.” In microglia from aged animals, there was a notable shift towards a higher prevalence of free-roaming microglia, characterized by c-Rel expression and sustained canonical NF-κB signaling. Interestingly, these two distinct microglial subpopulations demonstrated different levels of efficiency in Aβ phagocytosis and c-Rel activation in response to Aβ. We found that microglia from AD model mice showed higher c-Rel expression than those from healthy mice. Notably, in AD model mice, microglia isolated from plaque-developing animals demonstrated lower efficiency in Aβ phagocytosis compared to those from younger mice without plaque development. Through live cell imaging of microglia exposed to Aβ and the assessment of biomarkers and intracellular amyloid beta in microglia, we aim to uncover important molecular mechanisms associated with aging, AD susceptibility, and resistance in individuals.

Scientific Focus Area: Immunology

This page was last updated on Tuesday, August 6, 2024

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Current Research Festival

  • 2025
  • 2024
    • General Schedule of Events
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    • NIH Early–Career Investigator Lectures
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    • General Schedule of Events
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