# Choroid plexus organoids mimic amyloid uptake at the blood-cerebrospinal fluid-barrier

## TL;DR

Choroid plexus organoids are used to study how the blood-cerebrospinal fluid barrier handles amyloid in Alzheimer's disease.

## Contribution

Introduces a human stem-cell derived model to study amyloid uptake at the blood-CSF barrier in Alzheimer's.

## Key findings

- Choroid plexus organoids mimic key features of the blood-CSF barrier.
- The model can be used to investigate how amyloid is transported and cleared by the choroid plexus.
- Transthyretin's role in amyloid clearance is highlighted as a potential target for further study.

## Abstract

The choroid plexus (ChP) is a specialised tissue of the central nervous system that produces cerebrospinal fluid (CSF), maintains cerebral homeostasis and forms the blood-CSF barrier (B-CSF-B), a key interface that regulates the exchange of substances between the blood and the brain. Despite its physiological importance, the involvement of the ChP in neurodegenerative diseases such as Alzheimer’s disease (AD), remains poorly understood. This is largely due to the reliance on murine models and the limited availability of human brain tissue. Recent advances in human stem-cell derived ChP organoids now offer a more physiologically relevant model to interrogate ChP role in human health and disease. Given that in AD pathology beta-amyloid (Aβ) accumulation has been linked to early disruption of brain barriers, studying the B-CSF-B is particularly relevant. Transthyretin (TTR), the predominant protein secreted by the ChP, is thought to play a role in the transport and clearance of Aβ, although its exact mechanisms are not yet fully elucidated. Here, we propose the use of ChP organoids to investigate the role of the B-CSF-B in amyloid uptake which may contribute to barrier dysfunction and disease progression in AD.