Alzheimer’s disease is often described in numbers: it affects millions of people, the number of cases is rapidly increasing, and the costs reach trillions of dollars. But for families, the experience is deeply personal. “It’s a slow bereavement,” says Cold Spring Harbor Laboratory professor Nicholas Tonks, whose mother has Alzheimer’s disease. “You lose that person little by little.”
A major focus of Alzheimer’s disease research is plaque buildup in the brain. These plaques are composed of amyloid beta (Aβ), a naturally formed peptide that can accumulate and cluster over time. These deposits are widely believed to play an important role in disease progression.
Targeting PTP1B to improve memory
Tonks, along with graduate student Yushin Sen and postdoctoral researcher Steven Ribeiro Alves, identified a potential new strategy. Their research shows that blocking a protein known as PTP1B can improve learning and memory in a mouse model of Alzheimer’s disease.
Dr. Tonks first discovered PTP1B in 1988 and has spent decades studying its role in health and disease. In this latest study, his team discovered that PTP1B interacts with another protein called spleen tyrosine kinase (SYK). SYK helps control microglia (brain immune cells), which are responsible for removing excess Aβ and other debris.
“As the disease progresses, these cells become exhausted and become less effective,” Sen says. “Our results suggest that PTP1B inhibition can improve microglial function and clear Aβ plaques.”
Connection between 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 circumstances are thought to contribute to the increasing global burden of Alzheimer’s disease. Since PTP1B is already considered a therapeutic target for metabolic disorders, this association strengthens the rationale for exploring PTP1B in the treatment of Alzheimer’s disease as well.
Aiming for more effective Alzheimer’s disease treatment
Current treatments for Alzheimer’s disease primarily focus on reducing Aβ accumulation, but the benefits are often limited for many patients. “Additional benefits may be obtained using PTP1B inhibitors that target multiple aspects of the pathology, including Aβ clearance,” says Ribeiro Alves.
The Tonks laboratory is currently 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 the progression of Alzheimer’s disease and improve patients’ quality of life,” he says. With PTP1B emerging as a promising target, this approach could help move us closer to that goal.
