A promising new approach in tackling Alzheimer’s disease

Researchers at the University of Leeds and Lancaster University have identified a potential new drug target for Alzheimer’s disease.

The enzyme, named PDE4B, was tested to see whether reducing its activity could rescue memory, brain function and inflammation seen in Alzheimer’s disease.

“Reducing the activity of the PDE4B enzyme had a profound protective effect on memory and glucose metabolism, despite no decrease in the number of amyloid plaques in the brain – a key feature of the disease,” said Dr Steven Clapcote, Lecturer in the School of Biomedical Sciences.

This raises the prospect that reducing PDE4B activity may protect against cognitive impairment not only in Alzheimer’s disease but also in other forms of dementia, such as Huntington’s disease.

The findings are published in the paper Protective effect of PDE4B subtype-specific inhibition in an App knock-in mouse model for Alzheimer’s disease in the Nature journal Neuropsychopharmacology.

PDE4B

PDE4B is an enzyme inside cells that breaks down a molecule known as cyclic AMP, which regulates a range of cellular processes.

It was first identified as a risk factor for the development of Alzheimer’s disease in Australia and caught the attention of the Leeds and Lancaster scientists for its potential ability to manage the progression of Alzheimer’s disease.

To understand its mechanisms, the researchers explored gene, protein and glucose levels in mice using cutting edge brain imaging and maze tests.

In these tests, the scientists identified memory impairments and reduced glucose utilisation in the brain, like that seen in Alzheimer's disease patients. These deficits were prevented in mice with genetically reduced PDE4B activity.

These results offer real hope for the development of new treatments that will benefit patients with Alzheimer’s disease in the future. The next stage is to test whether PDE4B inhibiting drugs have similar beneficial effects.

The research is supported by Dunhill Medical Trust, BBSRC, Alzheimer’s Research UK, and the Scientific and Technological Research Council of Turkey.

Image by Milad Fakurian from Unsplash.