Neurocognitive disorders

 

Ongoing Research Projects

Early Tau Aggregation in Locus Coeruleus (LC) Neurons

Investigating Age-Dependent Synaptic Stress and Tau Pathology

This project explores the mechanisms behind the selective vulnerability of locus coeruleus (LC) neurons to tau pathology, a hallmark of early neurodegenerative processes, including Alzheimer's disease. We hypothesize that:

- Early tau accumulation in LC axons results from compromised proteostasis during the postnatal, age-dependent formation and pruning of coeruleo-cortical synapses.

- Tau pretangles in LC terminals co-localize with markers of active proteostasis, such as tau ubiquitination, TIA1-positive stress granules, unfolded protein response markers (BiP, pPERK, IRE1).

- Tau pathology is influenced by LC neuronal activity, which will be experimentally manipulated using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) and optogenetics.

This research may contribute to the early detection and intervention of tau-related neurodegenerative diseases.

Biomarker-Assisted Diagnosis of Dementia and Cognitive Disorders

Advancing Early Detection of Neurodegenerative Diseases with Biomarker Research

Early detection of neurodegenerative diseases like Alzheimer's disease has never been more critical. At our laboratory, we specialize in biomarker-assisted early diagnosis of neurocognitive disorders, with a strong emphasis on fluid biomarkers such as plasma and cerebrospinal fluid (CSF) markers.

In close collaboration with the Laboratory of Medical Chemistry (led by Associate Professor Aurélie Ladang), our research focuses on the development and clinical validation of plasma and CSF biomarkers. Our main goals are:

- Differentiating Alzheimer's disease from other cognitive disorders and from non-neurological causes of cognitive complaints, such as mood and psychiatric conditions.

- Enabling the earliest possible diagnosis of Alzheimer's disease in symptomatic patients.

- Evaluating the prognostic value of biomarkers in tracking the progression of Alzheimer's disease over time.

In 2025, our work is particularly focused on the study of plasma pTau217 and neurofilament light chain (NfL) biomarkers, which show great promise for early and accurate detection.

Future Directions: Building a Fluid Biobank for Neurodegenerative Diseases
Looking ahead, we plan to establish a dedicated fluid biobank for patients with neurodegenerative disorders, supporting future breakthroughs in research, diagnosis, and innovative treatments.

Join us as we push the frontiers of early diagnosis and precision medicine for neurodegenerative diseases.

High-Field MRI Biomarkers for Early Detection of Frontotemporal Dementia (FTD) in Amyotrophic Lateral Sclerosis (ALS)

Combining Neuroimaging and Genetics for Preclinical Diagnosis

ALS and FTD represent opposite ends of a shared neurodegenerative spectrum characterized by motor dysfunction and cognitive-behavioral decline. A common genetic driver of both conditions is the C9orf72 hexanucleotide expansion, which leads to the accumulation of toxic proteins such as poly-dipeptides and TDP-43 inclusions

Up to 50% of ALS patients develop executive dysfunction, and 15% meet the diagnostic criteria for FTD. Conversely, FTD often presents as behavioral disorders or language impairments, leading to misdiagnosis and delayed care.

Our project leverages 7 Tesla Histo-MRI, an advanced imaging modality that quantifies the physical and macromolecular properties of brain tissues in vivo. We aim to:

- Detect early microstructural alterations in the prefrontal cortex of ALS patients before cognitive symptoms emerge.

- Correlate imaging results with neuropsychological, clinical, and neurophysiological data.

- Identify reliable imaging biomarkers for preclinical FTD detection, aiding earlier diagnosis and intervention.

This research is crucial for adapting clinical care and supporting the deployment of emerging therapies, including antisense oligonucleotide (ASO) treatments.

LICORNE project ( Liège Cohort Research of Neurodegenerative Evolution)

Building a Longitudinal Cohort to Advance Neurodegenerative Disease Research

We are actively developing an observational, longitudinal, and prospective cohort of patients diagnosed with neurodegenerative disorders, spanning all stages — from subjective cognitive decline to late-stage dementia.

For each participant, we systematically collect:

- Blood samples

- Cerebrospinal fluid (CSF) samples

- Comprehensive clinical assessments

- Advanced imaging data

These data are gathered throughout the participants' follow-up period to ensure robust, real-time insights into disease progression.

Our goal is to build a comprehensive longitudinal databank that will empower future retrospective studies and drive major advances in understanding the pathophysiology and progression of neurodegenerative diseases.

This initiative is a critical step toward developing better diagnostic tools, prognostic models, and therapeutic strategies for conditions such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and others.