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Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary

Plasma exchange (PE) reduced amyloid plaques and brain inflammation in mice with advanced Alzheimer's disease (AD). This suggests PE may help clear amyloid-beta (Aβ) from the brain, warranting further investigation for AD treatment.

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Area of Science:

  • Neuroscience
  • Immunology
  • Biochemistry

Background:

  • Alzheimer's disease (AD) is the primary cause of dementia, characterized by amyloid plaques, neurofibrillary tangles, and neuroinflammation.
  • Current AD therapies targeting amyloid plaques have limitations in eligibility and risk-benefit profiles.
  • Peripheral strategies are being explored for their potential to impact brain Aβ and tau pathology, and neuroinflammation.

Purpose of the Study:

  • To investigate the efficacy of plasma exchange (PE) in reducing amyloid pathology and neuroinflammation in a mouse model of AD.
  • To assess the impact of PE on amyloid-beta (Aβ) deposition and inflammatory markers in the brain and plasma.

Main Methods:

  • Monthly PE procedures were administered to APP/PS1 mice starting at 11 months of age.
  • Histological analyses quantified amyloid deposits (Thioflavin-S, 4G8) and neuroinflammation markers (Iba-1, GFAP).
  • ELISA and Luminex assays measured Aβ levels and cytokine concentrations in brain homogenates and plasma.

Main Results:

  • PE significantly reduced amyloid plaque number and area in the cortex of treated mice.
  • PE decreased microglial (Iba-1) and astrocyte (GFAP) activation in the brain.
  • Biochemical analyses revealed lower insoluble Aβ1-40 and Aβ1-42 levels in PE-treated mouse brains, alongside modulated inflammatory cytokine profiles.

Conclusions:

  • Plasma exchange demonstrates potential in reducing brain amyloid burden and modulating neuroinflammation in an advanced AD mouse model.
  • Increased plasma Aβ levels post-PE suggest a mechanism of Aβ clearance from the brain to the periphery.
  • Further research is necessary to fully elucidate the mechanisms of Aβ clearance and anti-inflammatory effects of PE.