Tau's role in maintaining balance in the brain

Tau's role in maintaining balance in the brain

The scientists help explain how reducing the protein tau can prevent abnormal brain activity associated with Alzheimer’s disease, autism, and epilepsy.

The researchers uncovered that reducing levels of the protein tau, which is known for its role in Alzheimer’s disease and other neurodegenerative conditions, changes excitatory and inhibitory cells in ways that make it harder for the brain to burst with overexcitation.

“Epilepsy can be associated with many brain disorders, including Alzheimer’s disease and autism,” says senior author of the study published in Cell Reports “We previously showed in mouse models that reducing tau levels makes the brain more resistant to epilepsy of diverse causes, but we have puzzled about the underlying mechanisms. Our recent findings shed light onto how tau reduction affects different types of brain cells involved in creating abnormal network activity.”

It is critical to preserve a balance between the activity of excitatory and inhibitory cells for the brain to process information, appropriately control movements, and perceive things as they really are, rather than in a distorted way.

“The diseases we’re interested in have in common that they cause an excitation-inhibition imbalance in the brain,” says the author.

The team discovered that reducing levels of tau impacts both excitatory and inhibitory cells, but in different ways. They showed that excitatory neurons that lack tau don’t fire as much, whereas inhibitory neurons that lack tau are more easily stimulated to fire.

Together, these effects reduce the excitation-inhibition ratio in brain networks, counteracting diseases that cause abnormal increases in that ratio. To return to the classroom example, the neural effects of reducing tau are the equivalent of making the students less rambunctious and the teachers more effective at supervising them.

Just like calm in the classroom facilitates learning, the calming effect of tau reduction on brain networks might improve the brain’s ability to perform its functions, especially when the calm is being disrupted by disease. The insights gained in the new study could help guide the development of novel therapies that target tau as a way of reducing abnormal brain activities in a range of neurological and psychiatric diseases.