Latest Discovery   |   Nov 29, 2022

Protein involved in Alzheimer's disease tau neurotoxicity identified

Alzheimer's disease is the most common type of dementia and affects ~55 million people worldwide. Aggregation of tau is a defining feature of Alzheimer’s disease. Recently, researchers at the Indiana University School of Medicine identified Bassoon, a scaffolding protein found in the brain, as an interactor and stabilizer of tau seeds.

The research team at the Indiana University School of Medicine led by Dr. Cristian Lasagna-Reeves and Dr. Pablo Martinez performed unbiased quantitative proteomics to identify interactors of tau seeds. After identifying Bassoon as an interactor, the team went on to show that it is also involved in tau neurotoxicity in Drosophila and mouse models.

“Our paper established that a small portion of tau is capable of propagating in human tauopathies, including Alzheimer’s disease. This small portion of tau, which represent no more than 8% of total tau in the brain, interacts with the presynaptic protein Bassoon, which enhances the propagating and seeding properties of tau and also stabilizes toxic tau aggregates”, said Dr. Pablo Martinez.

Dr. Martinez and his colleagues utilized Adeno-associated virus (AAV) and vectors produced at VectorBuilder. Construction of the AAV vectors and AAV packaging was enabled by VectorBuilder’s Vector Design Studio. VectorBuilder offers superior quality AAV single-stranded and self-complementary vector cloning and packaging for your research and clinical needs.

“I have been working with VectorBuilder from the beginning of my postdoc. I’ve chosen VB because of the online platform to create customized vectors. It is really impressive how easy it is to digitally clone and the order process. Specifically, in our paper, we’ve used VB for several critical experiments, including the downregulation of Bassoon protein (AAV-shRNA) and to study the role of Bassoon in the propagation of tau (AAV-GFP-P2A-hTau). These experiments were extremely important to probe our hypothesis”, Dr. Martinez further elaborated.

Overall, this study provides insight into the mechanism of neurotoxicity in Alzheimer’s disease and other tauopathies and could translate into targeted therapies in the future.  

Source: Martinez, P., Patel, H., You, Y. et al. Bassoon contributes to tau-seed propagation and neurotoxicity. Nat Neurosci (2022).

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