Convergence of tau and TDP-43 in Alzheimer's: towards a multitarget diagnosis

Alzheimer’s disease (AD) is the leading cause of dementia in people over 65 years of age. AD is neuropathologically characterized by senile plaques and tau neurofibrillary tangles. TDP-43 was also discovered to accumulate in the majority of AD cases. Recently, we showed that TDP-43 assumes distinct molecular patterns of pathology in AD cases. These patterns were associated to distinct clinical features. We also found that TDP-43 interacts with tau in pre-clinical and symptomatic AD. In this project, we aim to investigate how the different TDP-43 patterns and interaction with tau impact the clinical diagnosis. Specifically, we want to: (1) determine tau and TDP-43 aggregation properties to identify potential therapeutic targets, (2) investigate tau and TDP-43 co-aggregation using an in vitro cell model and in vivo transgenic mouse models and (3) investigate tau biomarkers and genetic risk profiles in AD patients.

Keywords:Alzheimer's, neuropathologies, co-agregation, biomarkers

Disciplines:Neurological and neuromuscular diseases, Cognitive neuroscience, Molecular and cell biology not elsewhere classified, Neurosciences not elsewhere classified