# Clearance of extracellular human amyloid-β aggregates in C. elegans by nutraceutical and pharmaceutical interventions

## TL;DR

Researchers found that combining quercetin and rifampicin can clear amyloid plaques in a worm model, suggesting potential new Alzheimer's treatments.

## Contribution

The study demonstrates that nutraceutical and pharmaceutical combinations can effectively clear extracellular amyloid-β plaques in a C. elegans model.

## Key findings

- Quercetin 350 µM and rifampicin 75 µM reduced extracellular amyloid plaque burden in C. elegans.
- Combining quercetin and rifampicin had a greater plaque-clearing effect than either drug alone.
- The transgenic C. elegans model LSD2104 was used to study extracellular amyloid aggregation.

## Abstract

Numerous anti-amyloid therapies have seen recent clinical development and approval, such as the monoclonal antibodies aducanumab and lecanemab. However, in Alzheimer’s disease patients, amyloid-β (Aβ) plaques are found embedded in the extracellular matrix and surrounded by collagens, which might hinder these antibodies from targeting the plaques. We reasoned that various different nutraceutical and pharmaceutical agents might induce collagen and extracellular matrix turnover and removal of these collagen-embedded amyloid-β (Aβ) plaques. To address this idea, here, we used a transgenic
C. elegans
strain,
LSD2104
, expressing fluorescent human Aβ
1-42
as an
in-vivo
model for secreted amyloid aggregation in the extracellular matrix. We performed a screen of various nutraceuticals and pharmaceuticals along with different combinations, and we found that quercetin 350 µM and rifampicin 75 µM successfully cleared the extracellular amyloid plaque burden compared to the 0.2% DMSO control group, with a combination of the two agents producing the maximum effect compared to either drug alone. These results may implicate the exploration of combination therapeutics of nutraceuticals and pharmaceuticals in the clearance of amyloid-β (Aβ) plaques in Alzheimer’s disease.