Attributions

Investigating TDP-43 Biology in Alzheimer’s Disease and other Dementias

Sandra O. Tomé, PhD Catholic University of Leuven

Mentor

Dietmar Thal, MD Catholic University of Leuven

Summary

We want to unravel the biological differences between Alzheimer’s Disease and other dementias - such as aggregation properties and biomarker profiles, in order to contribute to patient stratification. 

Project Details

Aim 1) We will screen demented cases with several TDP-43 antibodies to investigate whether these diseases present similar/different TDP-43 species. We will use biochemical analysis to validate these results. Aim 2)We will use atomic-force microscopy to decipher specific TDP-43 and tau protein polymorphisms among these diseases. We will clarify whether these proteins’ structures change between distinct dementias. Aim 3)We want to estimate the presence of TDP-43 pathology using distinct biomarker profiles. We will use brain, blood and CSF samples to measure AD biomarkers through ELISA assays. 

In this, project, we will analyze molecular features of TDP-43 and tau proteins in Alzheimer’s Disease and LATE, a recently-defined disease entity. Moreover, we will use state-of-the-art technology – atomic force microscopy – to identify specific protein strains that could represent future therapeutic targets. We will also correlate specific biomarker and genetic profiles with the presence or absence of TDP-43. This research will contribute to patient stratification in the clinical setting for more personalized treatments for dementia. This is important because co-pathologies (here TDP-43 lesions) are often missed since to date there are no successful approaches in detecting TDP-43 pathology during life.