The long-debated question in Alzheimer’s research is why some brain cells are more susceptible to degenerative damage than others. Now, scientists at the University of California in Los Angeles (UCLA) and UC San Francisco have made an astounding discovery.

They’ve identified a natural cleanup system that removes harmful tau clumps in the brain before they can cause damage. Tau is the most common protein that aggregates in the brain of those suffering neurodegenerative diseases.

According to Science Daily, this discovery along with the emergence of a new mechanism that helps prevent the formation of toxic tau fragments, paves the way for new treatments for Alzheimer’s, an incurable disease that affects 7.2 million Americans over the age of 65.

The study, published in the journal Cell, used a novel CRISPR-based genetic screening on lab-grown human cells to analyze how tau protein accumulates in the brain. These toxic clumps of tau kill neurons and lead to neurodegenerative diseases.

The scientists identified a protein complex called CRL5SOCS4 that plays a crucial role in regulating tau cells by targeting harmful tau proteins for degradation.

It acts as part of the brain’s natural defense system, helping to prevent the accumulation of toxic tau fragments that are linked to neurodegenerative diseases like Alzheimer’s. By removing these tau clumps before they can cause damage, CRL5SOCS4 contributes to maintaining healthy brain function and may be an important target for future therapeutic strategies.

When the researchers analyzed the brain tissue of Alzheimer’s’ patients, they found that higher levels of CRL5SOCS4 also made neurons more likely to survive despite the accumulation of tau protein.

The second discovery involved the surprise connection between the dysfunction of energy-producing cells called mitochondria and the formation of NTA-tau, a tau fragment found in the blood and spinal fluid of Alzheimer’s patients.

The researchers said that this fragment appears to be generated when cells experience oxidative stress. In turn, this stress that is triggered by aging and neurodegeneration, reduces the efficiency of the proteasome.

The proteasome is a large protein complex found in cells that functions as a molecular machine to break down and recycle damaged, misfolded, or unnecessary proteins. By degrading these proteins into smaller peptides, the proteasome helps maintain cellular health and regulates various biological processes, including the removal of potentially toxic protein aggregates like those involved in neurodegenerative diseases such as Alzheimer’s.

According to a UCLA news release, these findings offer hope for new treatments to treat neurodegenerative diseases.

Enhancing CRL5SOCS4 activity could help neurons clear tau more effectively, while strategies to maintain proteasome function during stress might prevent the formation of toxic tau fragments.

“What makes this study particularly valuable is that we used human neurons carrying an actual disease-causing mutation,” said first study author Avi Samelson, assistant professor of neurology at UCLA Health. “These cells naturally have differences in tau processing, giving us confidence that the mechanisms we identified are relevant to human disease.”