# Inhibition of Amyloid β Accumulation by Protease-Digested Whitebait (Shirasu) in a Murine Model of Alzheimer’s Disease

## TL;DR

This study shows that protease-digested whitebait can reduce amyloid buildup in a mouse model of Alzheimer's disease, suggesting it may help prevent the condition.

## Contribution

The study identifies protease-digested whitebait as a novel functional food ingredient with potential to prevent Alzheimer’s disease.

## Key findings

- Protease-digested whitebait significantly inhibited BACE1 activity more than other seafood samples.
- WPD reduced insoluble amyloid β1–42 content in the cerebral cortex of 5xFAD mice.
- WPD administration decreased glial fibrillary acidic protein expression, indicating reduced astrogliosis.

## Abstract

The number of people with dementia is increasing annually worldwide. Alzheimer’s disease (AD), which accounts for the highest percentage of dementia-causing diseases, remains difficult to cure, and prevention of its onset is important. We aimed to discover new AD-preventive ingredients and investigate the inhibitory effects of ten different species of seafood digests prepared by protease treatment on β-secretase 1 (BACE1) activity. Substantial inhibition of BACE1 activity was observed in five species of seafood, and protease-digested whitebait (WPD) showed the highest inhibitory effect among the ten marine samples. We further examined the potential of WPD as an AD preventive component using a familial AD strain (5xFAD) murine model. The intraperitoneal administration of WPD for 28 days substantially decreased the insoluble amyloid β1–42 content and the expression of glial fibrillary acidic protein, a marker of astrogliosis, in the cerebral cortex of the 5xFAD mice. These results strongly suggest that WPD is a novel functional food-derived ingredient with preventive effects against AD.