Elizabeth J. Coulson, Australia

University School of Biomedical Sciences
Professor Elizabeth (Lizzie) Coulson graduated her PhD on the normal function of the amyloid precursor protein of Alzheimer’s disease, with now Emeritus Professor Colin Masters from the University of Melbourne. Following a year at the ZMBH, University of Heidelberg, Germany, she pursued postdoctoral work studying neuronal cell death in neurodegeneration and development at the Walter and Eliza Hall Institute with now Emeritus Professor Perry Bartlett before being recruited in 2003 to the University of Queensland as a founding member of the Queensland Brain Institute (QBI). She was appointed Professor in 2015, joining the School of Biomedical Sciences and becoming Deputy Head of School in 2019 and Interim Head in 2020. She maintains a 20% QBI appointment and is a member of QBI’s Clem Jones Centre for Ageing Dementia Research.

Presenter of 2 Presentations

 Conference Calendar

LIVE DISCUSSION

Session Name
LIVE DISCUSSION - CHOLINERGIC MECHANISMS IN AD AND PD
Session Type
LIVE SYMPOSIUM DISCUSSION
Date
10.03.2021, Wednesday
Session Time
16:00 - 16:30
Room
Live Symposia Discussion B
Lecture Time
16:00 - 16:30
Presenter
Session Icon
Live

CHOLINERGIC BASAL FOREBRAIN DEGENERATION DUE TO OBSTRUCTIVE SLEEP APNOEA INCREASES ALZHEIMER’S PATHOLOGY IN MICE

Session Name
CHOLINERGIC MECHANISMS IN AD AND PD
Session Type
SYMPOSIUM
Date
10.03.2021, Wednesday
Session Time
10:00 - 12:00
Room
On Demand Symposia B
Lecture Time
10:15 - 10:30
Presenter
Session Icon
On-Demand

Abstract

Aims

Epidemiological studies indicate that obstructive sleep apnoea is a strong risk factor for the development of Alzheimer’s disease but the mechanisms of the risk remain unclear.

Methods

We developed a method of modelling obstructive sleep apnoea in mice that replicates key features of human obstructive sleep apnoea: altered breathing during sleep, sleep disruption, moderate intermittent hypoxemia and cognitive impairment.

Results

When we induced obstructive sleep apnoea in a familial Alzheimer’s disease model, the mice displayed exacerbation of cognitive impairment and pathological features of Alzheimer’s disease, including increased levels of amyloid-beta and inflammatory markers, as well as selective degeneration of cholinergic basal forebrain neurons. These pathological features were not induced by chronic hypoxia or sleep disruption alone. Our results also revealed that the neurodegeneration was mediated by the oxygen-sensitive p75 neurotrophin receptor and hypoxia inducible factor 1 alpha activity. Furthermore, restoring blood oxygen levels during sleep to prevent intermittent hypoxia prevented the pathological changes induced by the OSA.

Conclusions

These findings provide a signalling mechanism by which obstructive sleep apnoea induces cholinergic basal forebrain degeneration and could thereby increase the risk of developing Alzheimer’s disease, as well as providing a rationale for testing a range of possible prophylactic treatment options for people with obstructive sleep apnoea and hypoxia including increased compliance of continuous positive airway pressure therapy.

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