Researchers explore how LRP1 regulates the spread of tau protein in neurodegeneration

A team of researchers at the University of California explored tau pathology and its implication in the development of neurodegenerative diseases. In their new study, released online in the peer-reviewed journal Nature, low-density lipoprotein receptor-related protein 1 (LRP1) was associated to the uptake and spread of tau in the brain.

The microtubule-associated protein tau is theoretically the underlying cause of several forms of dementia, such as frontotemporal dementia, Alzheimer’s disease, and chronic traumatic encephalopathy.

According to the findings, LRP1 plays a major role in the uptake and spread of tau, however, the underlying cellular mechanisms associated with tau has yet to be thoroughly studied.

“Here we show that the low-density lipoprotein receptor-related protein 1 (LRP1) controls the endocytosis of tau and its subsequent spread. Knockdown of LRP1 significantly reduced tau uptake in H4 neuroglioma cells and in induced pluripotent stem cell-derived neurons,” the findings state.

“The interaction between tau and LRP1 is mediated by lysine residues in the microtubule-binding repeat region of tau.”

In the study, the use of rodents in their experiments led to the conclusion that a decrease of LRP1 resulted in reduced propagation of tau between neurons, researchers affirmed.

“Furthermore, downregulation of LRP1 in an in vivo mouse model of tau spread was found to effectively reduce the propagation of tau between neurons,” the study concluded.

“Our results identify LRP1 as a key regulator of tau spread in the brain, and therefore a potential target for the treatment of diseases that involve tau spread and aggregation.”

Image courtesy of Gerry Shaw / Wikimedia