# Morphological and Molecular Characteristics of Choroid Plexus Epithelium in Aged Brains

## TL;DR

This paper explores how the choroid plexus in aging brains changes structurally and molecularly, linking these changes to observable enlargement seen in brain imaging.

## Contribution

The paper introduces a sequential degenerative model of choroid plexus epithelium aging, integrating morphological and molecular evidence.

## Key findings

- Choroid plexus enlargement in aging is linked to epithelial cell loss and compensatory hypertrophy.
- Mitochondrial remodeling and barrier dysfunction contribute to choroid plexus enlargement.
- SPINT1 and E-cadherin alterations may initiate epithelial instability in aging.

## Abstract

The choroid plexus (CP) has traditionally been regarded as a cerebrospinal fluid-producing structure; however, increasing evidence indicates that it functions as a dynamic regulatory interface involved in immune surveillance, metabolic homeostasis, and brain clearance. Neuroimaging studies consistently report CP enlargement across aging and diverse neurological and neuropsychiatric disorders, yet the underlying cellular mechanisms remain poorly integrated. In this review, we synthesize morphological, molecular, and imaging evidence to propose a sequential degenerative model of the CP epithelium. This model comprises: (1) regulated epithelial cell loss via apical extrusion, (2) compensatory hypertrophy of residual cells, (3) mitochondrial remodeling with oncocytic-like change, and (4) progressive blood–cerebrospinal fluid barrier dysfunction. At the molecular level, alterations in epithelial adhesion systems—particularly SPINT1-mediated protease regulation and E-cadherin–based adherens junction stability—may initiate epithelial instability. Hypertrophic epithelial cells exhibit increased mitochondrial burden, reflected by Tom20 expression, which may initially support metabolic adaptation but ultimately contribute to oxidative stress and functional decline. At the macroscopic level, the cumulative effects of cell loss, hypertrophy, and mitochondrial remodeling likely underlie CP enlargement detectable by magnetic resonance imaging. This framework positions CP enlargement as an imaging-visible manifestation of epithelial stress and provides a structural–molecular basis for interpreting CP alterations in brain aging and neurodegenerative disorders.