Alzheimer's Research Foundation supports three ULiège research projects with 600,000 euros


From left to right: Michel Georges (Director of the GIGA), Laurent Nguyen, Ira Espuny Camacho, Fabienne Collette, Joost Martens (Director of the Alzheimer Research Foundation), Emma Delhaye and Eric Salmon (Director of the Cyclotron Research Center).

The Alzheimer's Research Foundation has selected the scientific projects of Fabienne Collette, Emme Delhaye, Ira Espuny Camacho and Laurent Nguyen, researchers at the GIGA of the University of Liège, and has just granted them 600,000 euros out of the 3,200,000 euros granted by the Foundation to all Belgian universities.

Fabienne Collette, Research Director at Fund for Scientific Research – FNRS and researcher at the GIGA CRC In Vivo Imaging, Aging & Memory group, has been awarded €250,000 for her project "Cognitive fatigue in Alzheimer's disease". Her study focuses on how fatigue affects cognitive efficiency in patients in the early stages of the disease. Indeed, a series of factors that contribute to fatigue are associated with the pathophysiology and characteristics of Alzheimer's disease.

Laurent Nguyen, Director of the GIGA-StemCells and the Molecular Regulation of Neurogenesis Laboratory, and Ira Espuny Camacho, Postdoctoral Researcher at Fund for Scientific Research – FNRS at the GIGA-StemCells, are also receiving 250,000 euros for their study "Modelling Alzheimer's disease with 3D human multicellular brain organoids". The project aims to develop an innovative in vitro "mini-brain" model of Alzheimer's disease using patient-induced pluripotent stem cells. The aim is to reveal early disease phenotypes and establish the basis for a new method in designing therapeutic approaches to Alzheimer's disease.

The Alzheimer's Research Foundation is also supporting Emma Delhaye, Postdoctoral Researcher at Fund for Scientific Research – FNRS at the GIGA CRC In Vivo Imaging, Aging & Memory group, with 100,000 euros for her project aimed at better characterising the nature of the memory disorders that occur at the onset of Alzheimer's disease, using advanced assessment tools.

"The Thematic Research Units of the GIGA Institute are proud to be part of the Belgian scientific community involved in Alzheimer's disease research," says Professor Eric Salmon, Medical Director of the Cyclotron Research Centre (GIGA CRC In Vivo Imaging) at ULiège. "The members of the Scientific Committee of the Alzheimer's Research Foundation are particularly pleased to appreciate the quality of the Belgian projects that are subjected to a rigorous evaluation by foreign experts every year."

In 2020, the Alzheimer Research Foundation, a Belgian non-profit organisation of public utility, awarded a record amount of 3,200,000 euros to 17 scientific research projects conducted within Belgian universities. "Despite the covid-19 crisis, our donors have understood that Alzheimer's research is more important than ever and we have had a good year", says Joost Martens, director of the Foundation.

In a few words, what is your research about ?

Emma Delhaye

I'm interested in how the very first symptoms in our cognitive functioning can indicate that Alzheimer's disease is starting to develop in the brain. Research has identified the brain regions where Alzheimer's disease neuropathology first develops, through the aggregation of abnormally phosphorylated tau proteins and the accumulation of beta-amyloid peptides. However, between the very beginning of the installation of AD-related neuropathology in targeted brain regions and the first cognitive symptoms that will lead to a clinical diagnosis, several years may pass, and the disease has already had time to progress.

The aim of my research is to identify whether, and if so in what form, there are very subtle cognitive symptoms that would indicate the installation of Alzheimer's disease-related neuropathology as soon as it appears in the brain, and therefore much earlier in the course of the disease than we are able to do at present. This would improve diagnosis.

For the moment, our main hypothesis concerning the nature of this early symptom is the idea that a lesion linked to the installation of the neuropathology of Alzheimer's disease in the brain would generate a difficulty in representing objects in a very precise, even unique, way.

Fabienne Collette

I am interested in the influence that mental fatigue can have on our cognitive functioning, for example by transiently reducing our attentional capacities. After conducting studies on adults of all ages, my interest turned to pathologies characterised by the presence of incapacitating fatigue on a daily basis (such as multiple sclerosis). It then seemed particularly appropriate to extend this research to Alzheimer's disease. Indeed, several characteristics of this disease have been associated with the occurrence of pathological fatigue, such as a decrease in serotonergic transmission, sleep disorders, the presence of depression or apathy.

In this research programme, the frequency of occurrence of physical and mental fatigue in Alzheimer's disease, as well as the link with other symptoms known to influence the experience of fatigue (e.g. the presence of sleep disorders and depressive affect), will be assessed. On this basis, I will determine whether the presence of a high state of mental fatigue will accentuate the cognitive impairments presented by the patients. I will also look at the brain regions whose modification is associated with the presence of a high state of fatigue.

The results obtained will eventually allow for better management of the daily life of patients with Alzheimer's disease, by making it possible to identify the situations most likely to induce fatigue, and therefore to avoid proposing activities (cognitive or other) to them at that time that could cause them difficulties.

Participating in these studies? We are continuously recruiting participants aged 18 to 85 to take part in the various studies carried out at the GIGA-CRC, either as part of research on normal cognitive functioning or as a "control" subject for patients. Anyone interested can contact the researchers by sending a message to agitude@uliege.be

Laurent Nguyen and Ira Espuny-Camacho

Laurent Nguyen: We are very grateful to the Alzheimer's Research Foundation for supporting the development of new research in the laboratory that will allow the use of the organoid as an innovative model for studying Alzheimer's disease. Dr Ira Espuny-Camacho will oversee the development of this research in the laboratory.

Ira Espuny-Camacho: I am interested in generating new human in vitro and in vivo models that allow the study of human-specific aspects of degenerative brain diseases, such as Alzheimer's disease. Classical AD mouse models do not allow the recapitulation of all important pathological features of the diseased brain, such as tau pathology and neurodegeneration, underlining the need for human models.

Thus, my previous work established the conditions for in vitro culture and differentiation of cortical neurons from human pluripotent stem cells, as well as establishing a new in vivo model of Alzheimer's disease via transplantation of human neurons into the mouse brain. This work revealed a higher sensitivity of human neurons to toxic amyloid beta species compared to their mouse counterparts. Interestingly, human neurons also showed early aberrant synaptic features that are the starting point and driver of this project.

The study of early pathological events in Alzheimer's disease is of particular interest to me as it may lead to the discovery of new therapeutic targets to combat the disease.

In this research project, together with Laurent Nguyen, we will generate a new in vitro 3D "mini-brain" model where human neurons and human glial cell subtypes will be derived from cells of Alzheimer's disease patients. This new in vitro model will recapitulate the essence of the diseased human brain and help to further dissect the early pathological mechanisms that may lead to synaptic pathology in the brains of AD patients

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