# Acute amyloid-β exposure disrupts insulin signaling in blood–brain barrier endothelial cell culture models

## TL;DR

Exposure to amyloid-beta disrupts insulin signaling in blood-brain barrier cells, potentially contributing to early Alzheimer's disease.

## Contribution

Demonstrates that Aβ40 acutely impairs insulin signaling in blood-brain barrier endothelial cells.

## Key findings

- Aβ40 reduced insulin-stimulated Akt activation and altered AMPK inhibition.
- Aβ42 did not alter Akt signaling but suppressed basal Akt activation.
- Findings support a model linking vascular Aβ exposure to early brain insulin resistance in AD.

## Abstract

Brain insulin resistance and cerebrovascular dysfunction emerge early in late-onset Alzheimer’s disease, but how amyloid-β (Aβ) disrupts insulin signaling at the cerebrovascular blood–brain barrier—a major site of insulin receptor signaling and transport into the brain—remains unclear.

We exposed two distinct human blood-brain-barrier endothelial cell models to soluble Aβ40 or Aβ42 for 1 h, followed by 100 nM insulin for 10 min. Protein and phosphoprotein responses were quantified by reverse-phase protein array, and differential expression was evaluated using linear models.

Aβ40 reduced insulin-stimulated Akt activation and converted insulin’s normal inhibition of AMPK into modest stimulation. Aβ42 did not alter insulin-stimulated Akt signaling but moderately suppressed basal Akt activation.

These findings suggest that Aβ40 acutely impairs insulin signal transduction in BBB endothelial cells, supporting a model in which vascular Aβ exposure contributes directly to the early development of brain insulin resistance in AD.