Researchers Discover Brain Molecule, VPS35, Can Clear Alzheimer’s Tau Tangles

For the first time, researchers have determined that a molecule called VPS35 can clear tau proteins, a hallmark of Alzheimer’s disease, in the brain. That’s according to a new study published in the journal Molecular Psychiatry.

Think of the molecule VPS35 as a quality control worker in the brain – it picks through and removes defective proteins from neurons. This VPS35 system protects the brain by getting rid of the gunk that would otherwise clog up the brain’s inner workings.

In people with Alzheimer’s disease (as well as other neurodegenerative conditions like Parkinson’s), VPS35 doesn’t work in the way that it should. It’s not as good at detecting and clearing those defective proteins.

One such protein, tau, amasses in the brain and causes damage in Alzheimer’s patients. Until now, researchers did not understand the relationship between tau and the VPS35 system, and whether VPS35 could impact tau accumulation in the brain.

“We asked specifically whether the VPS35 system is important for clearing defective tau proteins,” explained senior investigator Domenico Praticò, MD, Scott Richards North Star Foundation Chair for Alzheimer’s Research, Professor in the Departments of Pharmacology and Microbiology, and Director of the Alzheimer’s Center at Temple at the Lewis Katz School of Medicine (LKSOM).

To figure this out, Praticò’s team looked at brain tissue from patients with progressive supra-nuclear palsy (PSP) or Picks’ disease. In PSP and Picks’ disease, tau is the only protein to form deposits in the brain, unlike Alzheimer’s disease, where both tau and beta-amyloid accumulate.

VPS35 Levels Directly Impact Tau Protein in Brain and Memory Issues

The researchers found that VPS35 levels in PSP and Picks’ patients were 50 percent lower than in healthy control subjects. When the scientists manipulated VPS35 levels in the lab, they discovered that they could control tau accumulation in tau-affected cells.

When they carried out further experiments in mice, lowering their VPS35 levels resulted in worsened memory, motor function and learning issues. It also significantly damaged neuron communication in the brain synapses. (This is where neurons meet and exchange signals, explained Praticò.)

According to Praticò, his next avenue of investigation will be whether they can use a drug to put VPS35 back to work to help clear tau tangles.

Past research has suggested that clearing tau tangles could help reverse or stop the progression of Alzheimer’s disease.

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