# A Single-Chain Variable Fragment Antibody Alleviates Inflammation and Apoptosis of Neurons by Inhibiting Tau Aggregation

## TL;DR

This study shows that a special antibody can reduce neuron damage and inflammation by preventing Tau protein clumps linked to Alzheimer's disease.

## Contribution

The study introduces a single-chain antibody that inhibits Tau aggregation both inside and outside neurons, reducing neurotoxic effects.

## Key findings

- Extracellular Tau aggregates cause intracellular Tau aggregation and increase ROS production.
- ScFv T1 inhibits Tau aggregation and reduces ROS accumulation, inflammation, and apoptosis.
- The findings support the development of new Alzheimer's therapies targeting Tau pathology.

## Abstract

Tau pathology is one of the main pathological features of Alzheimer’s disease (AD). Intracellular Tau may be released to the extracellular space upon neuron degeneration, where it has the potential to be toxic to other neurons. The propagation of Tau pathology, mediated by extracellular Tau aggregates, may underlie the pathogenesis of AD. Antibody therapies targeting Tau proteins are, therefore, considered highly promising. In this study, the cytotoxicity of extracellular Tau aggregates on SH-SY5Y cells was examined. The effect of extracellular Tau aggregates on intracellular Tau aggregation was also studied using a FRET-based assay. The extracellular Tau aggregates were found to cause intracellular Tau aggregation after entering the cells; meanwhile, ROS (reactive oxygen species) induced by Tau aggregates facilitated this process. A single-chain variable fragment antibody (scFv T1) inhibits Tau aggregation both extracellularly and intracellularly. ScFv T1 also inhibited the accumulation of ROS and alleviated the inflammation and apoptosis induced by Tau aggregates. These findings could provide experimental support for the study of neurotoxicity and related mechanisms of extracellular Tau aggregates, in addition to providing insights into the development of novel therapeutic agents to treat AD.