For families living with Alzheimer’s, the numbers only tell part of the story. “It’s a slow bereavement,” says Cold Spring Harbor Laboratory Professor Nicholas Tonks, whose mother lived with Alzheimer’s. “You lose the person piece by piece.”

Researchers at Cold Spring Harbor Laboratory say they have identified a new potential treatment strategy by blocking a protein called PTP1B.

In a mouse model of Alzheimer’s disease, the team found that blocking PTP1B improved learning and memory.

A major focus in Alzheimer’s research has been plaque buildup in the brain. The plaque is made of amyloid-β, or Aβ, a peptide that forms naturally but can accumulate and cluster over time. These deposits are widely believed to play a key role in driving the disease.

Tonks, graduate student Yuxin Cen and postdoctoral fellow Steven Ribeiro Alves found that PTP1B interacts with another protein called spleen tyrosine kinase, or SYK.

SYK helps control microglia, the brain’s immune cells, which clear debris including excess Aβ. “Over the course of the disease, these cells become exhausted and less effective,” Cen says. “Our results suggest that PTP1B inhibition can improve microglial function, clearing up Aβ plaques.”

The researchers say Alzheimer’s disease is also strongly associated with obesity and type 2 diabetes, which are recognised risk factors. PTP1B is already considered a therapeutic target for metabolic disorders, and the team says that strengthens the case for studying it in Alzheimer’s treatment.

Current Alzheimer’s therapies largely focus on reducing Aβ buildup, but the researchers say their benefits are often limited for many patients.

“Using PTP1B inhibitors that target multiple aspects of the pathology, including Aβ clearance, might provide an additional impact,” Ribeiro Alves says.

The Tonks lab is now collaborating with DepYmed, Inc. to develop PTP1B inhibitors for several medical applications.

For Alzheimer’s disease, Tonks said he sees these inhibitors being used alongside existing approved drugs. “The goal is to slow Alzheimer’s progression and improve quality of life of the patients,” he says.

The findings were published in Proceedings of the National Academy of Sciences.

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