Limiting the PTP1B enzyme could slow memory loss in Alzheimer’s, pointing to a potential treatment route, new research suggests.
The enzyme appears to contribute to memory decline in mice by altering how the brain’s immune cells behave, researchers say.
Dialling down PTP1B let microglia clear the protein clumps linked to Alzheimer’s, known as amyloid-beta plaques. Microglia are the brain’s resident immune cells that remove waste.
The study was conducted at Cold Spring Harbor Laboratory, a non-profit in New York, where professor Nicholas Tonks has examined the enzyme since discovering PTP1B in 1988.
Microglia normally sweep up waste in the brain but become less effective as Alzheimer’s, which slowly damages memory and thinking, advances.
The research suggests that PTP1B interacts with spleen tyrosine kinase (SYK), which helps control how microglia respond to damage and remove amyloid-beta.
“Over the course of the disease, these cells become exhausted and less effective,” said Yuxin Cen, the study lead.
“Our results suggest that PTP1B inhibition can improve microglial function, clearing up Aβ plaques,” Cen added.
PTP1B is already known to play a role in metabolic conditions such as obesity and type 2 diabetes, both recognised risk factors for Alzheimer’s disease.
The laboratory is now working to develop PTP1B inhibitors for multiple applications.
For Alzheimer’s disease, Tonks envisages a combination of therapies pairing existing approved drugs with PTP1B inhibitors.
According to the World Health Organisation, cholinesterase inhibitors such as donepezil are currently used to treat Alzheimer’s disease, while NMDA receptor antagonists such as memantine are prescribed for more advanced stages.
“The goal is to slow Alzheimer’s progression and improve the quality of life of the patients,” said Tonks.
More than 55 million people live with dementia globally, with Alzheimer’s disease accounting for up to 70 per cent of cases, according to the WHO.
“It’s a slow bereavement,” said Tonks, whose mother lived with Alzheimer’s.
“You lose the person piece by piece.”