Alzheimer’s gradually transforms memories into gray areas, for patients and their loved ones. “It’s a slow mourning,” says Professor Nicholas Tonks of Cold Spring Harbor Laboratory, whose mother lived with Alzheimer’s disease. “You lose the person piece by piece“. Behind this intimate pain, science is looking for ways to slow down this slide.
A team from Cold Spring Harbor Laboratory has identified a new way to slow down memory loss linked to the Alzheimer’s disease. In a study published on February 2, 2026 in
Proceedings of the National Academy of Sciencesresearchers show that blocking an enzyme called
PTP1B improves learning, memory and reduces plaques in the brains of mice with an Alzheimer’s model. All by targeting the brain’s immune system.
Alzheimer’s: why memory loss is so difficult to stop
In this pathology, protein deposits called
amyloid plaques accumulate between neurons and are linked to cognitive decline. Normally, immune cells, microgliaplay garbage collectors and eliminate this waste. “During disease, these cells become exhausted and less efficient,” said Yuxin Cen, graduate student and author of the study.Our results suggest that inhibition of PTP1B can improve microglial function, clearing amyloid plaques.”. Restarting this cleaning appears here as a way to preserve memory.
The PTP1B enzyme, discovered in 1988 by Nicholas Tonks, was best known for its role in type 2 diabetes and obesity. These metabolic disorders are among the well-established risk factors for Alzheimer’s disease. Seeing the same molecule involved in both metabolism and memory gave researchers a unique target to explore.
Blocking the PTP1B enzyme: how the memory of Alzheimer’s mice was protected
To test this idea, the team used APP/PS1 mice, which develop amyloid plaques and memory problems reminiscent of those of patients with age. By genetically deleting PTP1B in microglia, these animals performed better on tests of learning and object recognition, while showing fewer amyloid-β deposits in the hippocampus. An experimental drug, DPM1003, which blocks PTP1B, then reproduced these effects in older mice already covered in plaques.
The researchers showed that PTP1B binds directly to a key protein, SYK kinase, which drives the ability of microglia to engulf waste. When PTP1B is active, it removes phosphate groups from SYK and acts as a brake. Once the enzyme is blocked, SYK stays on, and the microglia start swallowing more amyloid plaques.
Towards combined treatments to slow memory loss
Tonks’ lab is collaborating with DepYmed to develop PTP1B inhibitors to complement existing treatments for
Alzheimer’s disease. For now, this work remains limited to mice and no drugs targeting PTP1B are available for patients.