Study reveals water's role in spread of Alzheimer’s-linked protein

A new study published in the journal PNAS and reported by Science Alert, conducted by researchers from Northwestern University and the University of California, has uncovered a possible mechanism explaining how the tau protein associated with Alzheimer’s disease and other forms of dementia spreads. The findings could pave the way for therapies aimed at slowing disease progression.

In the brains of Alzheimer’s patients, the proteins amyloid-beta and tau behave abnormally. However, scientists have yet to determine whether these changes are a direct cause of the disease or a consequence of it.

Tau protein plays a central role in this process, as it can adopt an abnormal shape and accumulate inside brain cells as threads known as fibrils, ultimately leading to nerve cell damage and death.

The researchers identified what they described as an "active site" in tau proteins—a hydrophobic region that helps the proteins bind together after surrounding water molecules are released. This initiates the formation of solid fibrils linked to declining brain function.

Songi Han, professor of physical chemistry at Northwestern University, explained that water molecules cannot fully cover this hydrophobic region, but instead form a stable shell that protects the protein and facilitates its interaction with similar proteins.

The team noted that fibril formation requires precise alignment of misfolded tau proteins, and any disruption in this alignment halts fibril growth. Experiments also showed that covering the "active site" with a chemical marker prevents further formation of these protein structures.

This discovery is particularly significant as it points to a potential therapeutic target for future drugs, which could disrupt a key stage that allows tau protein to spread from one nerve cell to another.

When cells containing fibrils die, these structures are released into the surrounding environment and move to other nerve cells, where the process repeats and contributes to the spread of the disease across different brain regions.

Han believes that identifying the site responsible for initiating tau aggregation gives scientists a chance to disrupt the misfolding process and prevent its transmission, which may help limit the progression of Alzheimer’s and some forms of dementia in the future.

The researchers suggested developing synthetic tau fibrils to study disease stages more precisely, emphasizing that a deeper understanding of how these structures form is a crucial step toward creating more effective treatments for neurodegenerative diseases.