Alzheimer's disease is often described in numbers, with millions of people affected, cases rising quickly, and costs reaching into the trillions. For families, however, the experience is deeply personal. "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."
A major focus in Alzheimer's research has been the buildup of plaque in the brain. This plaque consists of amyloid-β (Aβ), a peptide that forms naturally but can accumulate and cluster together over time. These deposits are widely believed to play a key role in driving the disease.
Targeting PTP1B To Improve Memory
Tonks, along with graduate student Yuxin Cen and postdoctoral fellow Steven Ribeiro Alves, has identified a new potential strategy. Their research shows that blocking a protein known as PTP1B can improve learning and memory in a mouse model of Alzheimer's disease.
Tonks first discovered PTP1B in 1988 and has spent decades studying its role in health and disease. In this latest work, his team found that PTP1B interacts with another protein called spleen tyrosine kinase (SYK). SYK helps control microglia (the brain's immune cells), which are responsible for clearing debris such as excess Aβ.
"Over the course of the disease, these cells become exhausted and less effective," says Cen. "Our results suggest that PTP1B inhibition can improve microglial function, clearing up Aβ plaques."
Links to Metabolism and Disease Risk
Alzheimer's disease is also strongly associated with obesity and type 2 diabetes, both of which are recognized risk factors. These conditions are thought to contribute to the growing global burden of Alzheimer's. Because PTP1B is already considered a therapeutic target for metabolic disorders, this connection strengthens the case for exploring it in Alzheimer's treatment as well.
Toward More Effective Alzheimer's Treatments
Current therapies for Alzheimer's disease largely focus on reducing Aβ buildup, but 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," says Ribeiro Alves.
The Tonks lab is now collaborating with DepYmed, Inc. to develop PTP1B inhibitors for several medical applications. For Alzheimer's disease, Tonks envisions combining these inhibitors with existing approved drugs. "The goal is to slow Alzheimer's progression and improve quality of life of the patients," he says. With PTP1B emerging as a promising target, this approach could help move closer to that goal.
