Piecing together the role of TDP43 in the Alzheimer’s disease puzzle

Alzheimer’s disease (AD) is a complex heterogenous neurodegenerative disorder characterised by amyloid beta plaques and tau protein tangles.
Recent evidence suggests that the protein TDP43 may play a significant role in the progression and severity of AD. TDP43 is now being found in a large proportion of AD patients and correlating with accelerated cognitive decline. This project aims to investigate the interactions between amyloid beta, tau and TDP43, and determine how pathological TDP43 contributes to the onset and progression of AD. This involves using adeno-associated viruses to regulate gene expression of abnormal TDP43 at different disease stages in AD mouse models. The integration of functional, molecular and histopathological analyses will provide a thorough understanding of how TDP43 mediates its effect in the presence of amyloid
beta and tau pathologies. This research would pave the way for novel therapies for AD targeting TDP43 processes, offering new avenues for intervention that might mitigate disease progression and improve patient outcomes. This project will offer critical insights into the interplay between multiple proteins in AD, underscoring the importance of TDP43 in disease
etiology and progression.