LAUSR

Alzheimer's disease (AD) and most of the other tauopathies are incurable neurodegenerative diseases with unpleasant symptoms and consequences. The common hallmark of all these diseases is tau pathology, but its connection with disease progress has not been completely understood so far. Therefore, uncovering novel tau interacting partners and pathology affected molecular pathways can reveal the causes of diseases as well as potential targets for the development of AD treatment. Despite the large number of known tau interacting partners, the limited number of studies focused on in vivo tau interactions in disease or healthy conditions are available. Here, we applied an in vivo crosslinking approach, capable of capturing weak and transient protein-protein interactions, to a unique transgenic rat model of progressive tau pathology similar to human AD. We have identified 175 potential novel and known tau interacting proteins by MALDI-TOF mass spectrometry. Several of the most promising candidates for possible drug development were selected for validation by coimmunoprecipitation and colocalization experiments in animal and cellular models. Three proteins, Baiap2, Gpr37l1 and Nptx1, were confirmed as novel tau interacting partners, and based on their known functions and implications in neurodegenerative or psychiatric disorders, we proposed their potential role in tau pathology. The MS data were deposited in the ProteomeXchange Consortium with the dataset identifier PXD018687 and 10.6019/PXD018687.