# Plasmalogens Alter the Aggregation Rate of Transthyretin and Lower Toxicity of Transthyretin Fibrils

## TL;DR

This study shows that plasmalogens can reduce the aggregation and toxicity of transthyretin fibrils, which cause heart disease.

## Contribution

The novel finding is that plasmalogens with specific fatty acid compositions alter TTR aggregation and fibril toxicity.

## Key findings

- Choline plasmalogens with saturated and unsaturated fatty acids strongly suppress TTR aggregation.
- Plasmalogens with unsaturated fatty acids lead to the formation of thicker TTR fibrils.
- Plasmalogens with C16:0, C18:0, and C18:1 fatty acids significantly reduce TTR fibril cytotoxicity.

## Abstract

Heart tissue can experience a progressive accumulation
of transthyretin
(TTR), a small four subunit protein that transports holoretinol binding
protein and thyroxine. This severe pathology is known as transthyretin
amyloid cardiomyopathy. Numerous experimental studies indicated that
the aggregation rate and toxicity of TTR fibrils could be altered
by the presence of lipids; however, the role of plasmalogens in this
process remains unknown. In this study, we investigate the effect
of choline plasmalogens (CPs) with different lengths and saturations
of fatty acids (FAs) on TTR aggregation. We found that CPs with saturated
and unsaturated FAs strongly suppressed TTR aggregation. We also found
that CPs with saturated FAs did not change the morphology of TTR fibrils;
however, much thicker fibrillar species were formed in the presence
of CPs with unsaturated FAs. Finally, we found that CPs with C16:0,
C18:0, and C18:1 FAs substantially lowered the cytotoxicity of TTR
fibrils that were formed in their presence.