Investigating TDP-43 biology in Alzheimer's Disease and LATE: Impact on the Clinical Diagnosis

Project Summary

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.