Neurodegenerative dementias represent a spectrum of age-related diseases that progressively and irreversibly impair cognitive and behavioral functions. These conditions are primarily attributed to the destabilization of protein homeostasis within the aging brain, underpinning disorders such as Alzheimer’s disease, Lewy body dementia, and frontotemporal lobar dementia. Despite the global prevalence exceeding 50 million individuals, effective treatments remain elusive. Within this broad category, tauopathies are distinguished by the abnormal accumulation and hyperphosphorylation of the tau protein, manifesting in conditions including Alzheimer's disease, corticobasal degeneration, progressive supranuclear palsy, and frontotemporal dementia. These diseases are characterized by their gradual, subtle onset and significant individual variability.
Conventional diagnostic methods, such as brain imaging and cerebrospinal fluid (CSF) sampling, are hindered by cost, invasiveness, and inability to map brain lesion topography longitudinally. Emerging research suggests that blood biomarkers for brain-derived proteins could offer a promising, cost-effective, and non-invasive alternative for earlier detection and treatment of these conditions. However, the utility of circulating protein assays in reflecting tauopathies' intricate topographical and subcellular nuances is limited. Despite extensive research spanning over eight decades, critical gaps in our understanding of Alzheimer's disease and tauopathies persist, potentially explaining the historical failures of therapeutic interventions.
Our research unit is committed to translational research that mirrors the clinical reality as closely as possible. It is in partnership with the Leenaards Memory Centre, renowned for its diagnostic expertise in cognitive decline. Our approach integrates clinical data, animal models, cell cultures, engineered viral vectors, advanced microscopy, proteomic analysis, post-mortem tissue studies, and patient-derived biofluids (plasma/CSF and saliva) with the following primary objectives:
Leveraging in vitro and in vivo projects alongside a human post-mortem biobank, we aim to unravel the mechanisms driving various protein pathologies and their propagation within the brain. In collaboration with AC Immune, we are exploring strategies to mitigate the effects of protein aggregation, supported by the doctoral work of Jeanne Espourteille, Luc Belinga, and Valentin Zufferey.
At the core of our research since 2021, in tight collaboration with the Leenaards Memory Centre, we've amassed an extensive dataset and biological samples from dementia patients since 2013. Current projects by Jeanne Espourteille, Aatmika Barve, and Luc Belinga are directed at dissecting symptom heterogeneity and identifying biofluid biomarkers (in saliva and blood) to foresee the subtype and progression of these diseases. We are mainly focused on isolating and characterizing brain-derived extracellular vesicles circulating in the body, a formidable challenge involves distinguishing these vesicles and decoding their contents. In partnership with Nikon Microsystem, we are developing a new solution for the visualization and phenotyping of circulating extracellular vesicles.
Additionally, as part of a Swiss-Cameroon initiative and Luc Belinga's PhD, we explore the utility of circulating biomarkers for diagnosing Alzheimer's disease in African populations.