Scientists discover how water may help trigger the spread of Alzheimer’s disease

Scientists from Northwestern University and the University of California, Santa Barbara, have identified an unexpected factor that may contribute to the spread of Alzheimer’s disease in the brain: water.

The researchers found that water molecules surrounding a specific “hotspot” on tau proteins play a key role in how these proteins become misshapen and clump together, forming toxic tangles that damage neurons.

Tau proteins normally help stabilize the internal structure of nerve cells. However, in diseases such as Alzheimer’s and frontotemporal dementia, these proteins can fold incorrectly and form abnormal aggregates.

The study, published in the journal Proceedings of the National Academy of Sciences (PNAS), identified a specific region of tau that repels water but remains surrounded by water molecules.

When two tau proteins approach each other at this location, water is released, generating energy that helps the proteins bind together and form rigid structures known as fibrils.

“You have a specific site, and the water cannot fully cover it because it doesn’t like water. But that part still needs to be protected, because otherwise the protein collapses and is no longer available,” said Songi Han, the study’s lead author.

Blocking the hotspot stopped fibril growth

Using laboratory experiments and computational models, the researchers found that chemically blocking the specific hotspot, located near amino acid 300, stopped the growth of tau fibrils.

By contrast, blocking other regions of the protein did not prevent the fibrils from continuing to grow.

The findings could help scientists develop drugs designed to block this anchoring site, potentially preventing tau proteins from binding together and contributing to disease progression.

The discovery could also help researchers create synthetic tau fibrils to study how Alzheimer’s and other dementias develop.

A step toward better disease models

Studying abnormal tau proteins remains challenging. Accessing the brains of living patients is difficult, while many disease-related processes have already stopped in donated brains examined after death.

“To cure a disease, you need to be able to recreate it,” Han said.

The researchers hope their findings will provide new ways to investigate tau aggregation and support future research into treatments. However, further studies are needed to determine whether targeting this mechanism can lead to effective therapies for patients.