Researchers from the University of Liège receive almost €1 million for their research on Alzheimer's disease

In Belgium, one in five people, and up to one in three women, will develop a form of dementia. Of the different manifestations of dementia, seven out of ten involve Alzheimer's disease. Moreover, due to the increasing ageing of the population, two million Belgians will be directly or indirectly affected by dementia in the future, making the disease a real societal challenge. However, there is still no drug or treatment capable of curing this disease.

Crucial research

"The University of Liège plays a leading international role in the understanding of Alzheimer's disease. We are therefore delighted to be able to award grants to three groups of researchers from ULiège for their research, which was particularly well evaluated by our committee of numerous Belgian and foreign professors during the selection process," explains Joost Martens, director of the Alzheimer Research Foundation.

Sleep as an element of prevention

Gilles Vandewalle, Fund for Scientific Research - FNRS Senior Research Associate at the GIGA CRC In vivo Imaging, receives a grant of €300,000 for his project "SLEEP-CONNECTION" aimed at studying brain connectivity during sleep in the preclinical neuropathology of Alzheimer's disease. The aim of the project is to show whether improving the quality of sleep can have a beneficial effect on the delay of Alzheimer's disease symptoms or even prevent it. 

Locomotor activity as a tool for early diagnosis

The group of Christina Schmidt, Fund for Scientific Research - FNRS Research Associate , and Grégory Hammad, Researcher, at the GIGA CRC In vivo Imaging has also been awarded a grant of €300,000 for research aimed at better understanding the links between the deregulation of locomotor activity and brain changes in Alzheimer's disease, which could lead to a tool for early diagnosis and monitoring of the disease.

A new human model for studying Alzheimer's disease

Ira Espuny Camacho, Associate Professor at GIGA Stem Cells, has been awarded a €300,000 grant for her study "A human brain organoid model to study the role of microglia in sporadic Alzheimer's disease", as well as the Young Research Award (€50,000). His project aims to better understand the role of microglial cells in the human brain in the early stages leading to sporadic Alzheimer's disease. The aim is also to discover new strategies to combat the disease using a multicellular organoid model (a miniaturised version mimicking the structure of the organ) of the human brain.
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In a few words, what is your research about?

Gilles Vandewalle: "The SLEEP-CONNECTION project aims to study the link between sleep and Alzheimer's disease (AD). Sleep quality deteriorates during aging and the degree of sleep degradation is related to the risk of developing AD, making sleep a promising new target for intervention to prevent or delay AD. However, a full understanding of the mechanisms involved is needed before designing an effective intervention. The main objective of SLEEP-CONNECTION is to identify how the activity of brain networks during sleep may contribute to the early neuropathology of AD. To achieve this goal, the ambitious project will take advantage of the high resolution 7 Tesla functional magnetic resonance imaging (7T fMRI) available at ULiège. The brain activity of 130 healthy adults aged 20 to 70 years will be recorded during wakefulness and sleep and linked to their genetic risk of developing AD. The project will provide fundamental insights into the role of sleep in early AD-related brain alterations and the brain dysfunctions during sleep that may shape AD trajectories over the life course."
Christina Schmidt and Grégory Hammad : "It is fascinating to see how some apparently simple and regular physiological processes such as heart or breathing rate or walking actually have a complex regulation, which takes place at different time scales. In Alzheimer's disease, this so-called 'fractal' regulation of locomotor activity is altered, sometimes several years before the first clinical symptoms of the disease. However, the mechanism of deregulation as well as its link with the underlying cerebral integrity remain poorly understood. The objective of our project is therefore to quantify the characteristics of the fractal regulation of locomotor activity and to link them to the structural and functional modifications of the brain involved in Alzheimer's disease. In the longer term, we hope to contribute to establishing the measurement of the regulation of this physiological signal as a tool for the early diagnosis and monitoring of Alzheimer's disease. This project is based on our respective expertise, human neuroscience and physics. This is why the collaboration that we have had for several years now has been essential in the development of this project and will, we hope, guarantee its success".
Ira Espuny Camacho: "The vast majority of patients with Alzheimer's disease have sporadic forms of the disease that do not carry mutations in the PSEN or APP genes, which are responsible for the familial genetic forms of the disease. Furthermore, genome-wide association studies (GWAS) have revealed the role of several genes that confer a higher risk of AD when they carry specific mutations or genetic variations. Interestingly, the expression of most of these genes is highly enriched in brain microglia cells, highlighting an important contribution of these cells to the pathology. This project aims to elucidate the role of brain immune cells, the microglia, in the early stages leading to neurodegeneration in the Alzheimer brain. In this project, we will study genes whose expression is altered in human microglia cells derived from patients with sporadic AD or following exposure to beta-amyloid species, in order to identify important genes/pathways affected early in the sporadic AD brain. In addition, candidate genes will be validated by gain- and loss-of-function approaches to understand the contribution of these molecular pathways to the mechanisms triggered in AD. To achieve our goals, my team is generating human pluripotent stem cell-derived microglia and human brain organoids that are co-cultured to develop a novel multicellular "mini-brain" organoid model. The aim is to understand the contribution of all brain cell types, and particularly microglia cells, in the early stages leading to pathology in the AD brain."

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