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Debomoy K Lahiri1,2, Bryan Maloney2, Calvert Schmued3

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|December 26, 2025
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Summary
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Phenanthroline-amine (PAA) significantly reduces amyloid plaques in Alzheimer

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Alzheimer's disease (AD) involves amyloid-β precursor protein (APP) and apolipoprotein E (APOE).
  • Neurotoxic amyloid fragments result from APP cleavage.
  • Metal chelators like phenanthroline-amine (PAA) show promise in reducing amyloid plaques.

Purpose of the Study:

  • To evaluate PAA's efficacy in reducing amyloid plaques in a double transgenic Alzheimer's disease mouse model.
  • To determine if PAA directly binds to amyloid plaques in tissue sections.

Main Methods:

  • APP/PS1 mice were orally administered PAA or a control vehicle.
  • Brain tissue sections were stained for amyloid plaques using hydroxyquinoline oxalate (HQ-O) and PAA.
  • Double labeling techniques were employed to compare PAA and HQ-O staining.

Main Results:

  • PAA treatment significantly reduced the number and size of amyloid plaques by 32.4% compared to controls.
  • PAA directly labeled amyloid plaques in tissue sections with red fluorescence.
  • PAA demonstrated more extensive plaque labeling than HQ-O.

Conclusions:

  • Chronic PAA administration effectively reduces amyloid plaque burden in a relevant Alzheimer's disease model.
  • PAA exhibits direct binding affinity for amyloid plaques.
  • Potential PAA targets include transition metals, glycosylated molecules (APOE, APP), and metalloproteases.