# Astrocytes at the crossroads of obstructive sleep apnea and Alzheimer’s disease: from oxygen sensing to neurodegeneration

## TL;DR

This review explores how astrocytes may connect obstructive sleep apnea with Alzheimer’s disease through oxygen sensing and neuroinflammation.

## Contribution

Highlights astrocytes as a novel mechanistic link between OSA and AD, focusing on their role in intermittent hypoxia and neurodegeneration.

## Key findings

- Astrocytes respond to intermittent hypoxia in OSA, potentially promoting oxidative stress and neuroinflammation.
- Maladaptive astrocyte responses may overlap with Alzheimer’s disease pathophysiology.
- Epidemiological evidence suggests a bidirectional relationship between OSA and AD.

## Abstract

Obstructive sleep apnea (OSA) is a highly prevalent sleep-related breathing disorder characterized by recurrent episodes of intermittent hypoxia and sleep fragmentation, and it has been increasingly linked to cognitive decline and Alzheimer’s disease (AD). Growing evidence suggests that vascular risk factors and sleep-related breathing disorders such as OSA may contribute to AD disease onset and progression. This review aims to explore astrocytes as a potential mechanistic link between OSA and AD.

A literature search was conducted in the PubMed database using combinations of keywords including “astrocytes,” “obstructive sleep apnea,” “intermittent hypoxia,” “sleep-disordered breathing,” “Alzheimer’s disease,” and “dementia”.. Epidemiological, mechanistic, and clinical studies addressing the interplay between astrocyte function, sleep-disordered breathing, and neurodegeneration were reviewed and synthesized.

Astrocytes are increasingly recognized as oxygen-sensing cells capable of responding to fluctuations in oxygen availability. Under conditions of intermittent hypoxia, such as those occurring in OSA, astrocytic responses may become maladaptive, promoting oxidative stress and neuroinflammatory signalling. These processes overlap with key aspects of AD pathophysiology and may contribute to both disease initiation and progression. Although available evidence remains heterogeneous and not fully conclusive, epidemiological studies suggest a bidirectional association between OSA and AD.

Glial maladaptation to intermittent hypoxia may represent a critical interface between sleep-disordered breathing and neurodegeneration. Targeting astrocyte-mediated mechanisms could offer new insights into the pathophysiological links between OSA and AD.