Researchers have discovered that the same protein that controls fat metabolism in the liver is also responsible for lowering abnormal clumps of proteins – called brain plaques – that block normal nerve cell communication leading to the Alzheimer’s disease.
A novel treatment combining lipid-lowering drugs that reduce plaque formation and a vitamin A derivative that stimulates that fat metabolizing protein eventually might be effective in treating the disease, the said.
“Understanding how plaques are formed is important to developing effective drugs that lower plaques and stop the progression of Alzheimer’s disease,” says Kalipada Pahan, professor of neurology at Rush University.
In Alzheimer’s, pieces of a protein called beta-amyloid clump together to form hard, insoluble plaques, which precede amyloid protein. In a healthy brain, this precursor protein is broken down by another protein, called ADAM10.
“Interestingly, neurons from mice lacking PPARalpha (the protein that controls fat metabolism in the liver) contain less ADAM10 compared to neurons from normal mice,” Pahan said.
The study findings indicate that mice lacking PPARalpha produce more of the plaque-forming beta-amyloid protein than normal mice. Not surprisingly, in an Alzheimer’s disease mouse model, the PPARalpha-deficient mice have more amyloid plaques in their brains and shorter life expectancies than normal mice.
This discovery may point to a possible treatment for Alzheimer’s utilizing gemfibrozil, an FDA-approved drug used to regulate certain lipids (fat molecules). “We have found that gemfibrozil and retinoic acid (a derivative of vitamin A) stimulate PPARalpha (the fat metabolism regulator), increase ADAM10 (the protein that breaks down plaque-causing proteins) and reduce amyloid plaques in the brains of the mouse model of Alzheimer’s disease,” Pahan says.
If the findings are replicated in Alzheimer’s disease patients, it would open up a promising avenue of treatment of this devastating neurodegenerative disease, he said. Alzheimer’s disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills, and eventually even the ability to carry out the simplest tasks.
In most people with Alzheimer’s, symptoms first appear after age 60. Alzheimer’s disease is the most common cause of dementia among older people and affects as many as 5.3 million people in the U.S. and it became famous with the former US President Ronald Reagan suffering from it during his last days.
The study’s findings were published June 15 in the scientific journal Proceedings of the National Academy of Sciences of the USA.