A compound discovered by scientists at NYU Langone Medical Center reduced by more than half levels of amyloid proteins in the brains of animals with Alzheimer's disease.
Long implicated in Alzheimer's, amyloid proteins clump together to form plaques. What's unknown is how these proteins accumulate in the central nervous system and to what extent they play a role in the neurodegenerative symptoms of the disease.
Investigators discovered that the compound, dubbed 2-PMAP, is nontoxic in mice, easily gets into the brain and lowers the production of amyloid β and associated amyloid deposits.
The researchers believe that a drug like 2-PMAP that could be taken daily over many years to gradually lower the production of amyloid β may be an effective prevention strategy for Alzheimer's.
"What we want in an Alzheimer's preventive is a drug that modestly lowers amyloid β and is also safe for long term use," says Dr. Martin Sadowski, associate professor of neurology, psychiatry, and biochemistry and molecular pharmacology, who led the research. "Statin drugs that lower cholesterol appear to have those properties and have made a big impact in preventing coronary artery disease. That's essentially what many of us envision for the future of Alzheimer's medicine."
Dr. Sadowski's team came across 2-PMAP after screening a library of compounds and finding that, even at low, nontoxic concentrations, the molecule significantly reduced production of amyloid β's mother protein, known as amyloid precursor protein (APP), in test cells and lowered amyloid beta levels by 50% or more.
The findings appear online in the journal Annals of Neurology.
Testing the compound in mice, the scientists found that 2-PMAP had a similar impact on animals engineered to have the same genetic mutations found in Alzheimer's patients with a hereditary form of the disease that causes overproduction of APP and Alzheimer's-like amyloid deposits. After being treated with 2-PMAP for 5 days, the mice had lowered levels of both APP and amyloid β in the brain.
Dr. Sadowski and his team are now working on modifying the compound to make it more effective and hope to eventually test the experimental therapy in people.
- here's the press release