Alzheimer's disease is often described in numbers - millions affected, cases rising, costs in the trillions. But for families, it's less a statistic and more a slow-motion horror show. "It's a slow bereavement," says Cold Spring Harbor Laboratory Professor Nicholas Tonks, whose mother lived with the disease. "You lose the person piece by piece." Cheerful stuff.
A major suspect in Alzheimer's has long been the buildup of amyloid-β (Aβ) plaques in the brain - gunk that accumulates like unwashed dishes in a college dorm. Now Tonks, graduate student Yuxin Cen, and postdoctoral fellow Steven Ribeiro Alves have found that blocking a protein called PTP1B can improve learning and memory in mouse models of the disease. Yes, mice. But it's a start.
Tonks first discovered PTP1B in 1988 and has since spent decades figuring out what it does. Turns out, PTP1B buddies up with another protein, spleen tyrosine kinase (SYK), which helps control microglia - the brain's immune cells that normally clean up 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." So basically, give the brain's janitors a pep talk.
Alzheimer's is also strongly linked to obesity and type 2 diabetes, both risk factors that are contributing to the global burden. Because PTP1B is already a therapeutic target for metabolic disorders, this connection makes it an even more appealing target. Kill two birds with one protein inhibitor.
Current Alzheimer's therapies mostly focus on reducing Aβ buildup, but their benefits are often disappointing. "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. Tonks envisions combining these with existing approved drugs. "The goal is to slow Alzheimer's progression and improve quality of life of the patients," he says. Which, you know, would be nice.