MGH Researchers Discover How Amyloid Beta Forms in the Brain

Amyloid beta (Abeta) is a protein that is believed to be at the root of
Alzheimer’s disease (AD). The neurotoxin forms in the axons, the threadlike fibers that carry information from one brain cell to another. As Abeta accumulates, it forms sticky plaques that interfere with cell-to-cell communication, causing problems with memory, thinking skills and other brain functions. Preventing plaque formation and stopping its progression have been the subjects of research efforts around the world for many years.

But in a major breakthrough, researchers at Massachusetts General Hospital (MGH) have discovered how Abeta forms. This insight could help in the development of therapies designed to prevent the accumulation of the harmful protein in the brain, says Rudolph Tanzi, PhD, vice chairman of Neurology and co-director of the McCance Center for Brain Health at MGH. Dr. Tanzi has spent decades studying the origins and progression of AD and is one of the world’s leading experts on the disease that affects more than 6 million Americans—a
number that is expected to double in less than 30 years.

“We knew that Abeta is made in the axons of the brain’s nerve cells, but we didn’t know how,” says Dr. Tanzi, who in 1986 led a team of researchers that discovered the first AD gene, which provides instructions for making amyloid beta precursor (APP). As enzymes cleave APP, one byproduct that forms is Abeta.

Most recently, Dr. Tanzi and his colleagues discovered that this process occurs in a part of the neuron called the mitochondria associated endoplasmic reticulum membranes (MAM). Though the exact nature of MAMs was unknown for many years, scientists had learned that the number and activity of MAMs were increased in people with AD.

In their study, published recently in Cell Reports, Dr. Tanzi and his team found that by altering MAM levels and activity through gene therapy or by using a drug that blocks the sigma-1 receptor (S1R)—a key protein in the MAM—the production of Abeta drops.

“Our results suggest that the sigma-1 receptor might be a viable therapeutic target for reducing Abeta production, specifically in axons,” Dr. Tanzi says.

He and other MGH researchers are looking at ways to inhibit the changes to the APP that lead to Abeta production and developing experimental treatments that prevent Abeta production in the MAMs.

The post MGH Researchers Discover How Amyloid Beta Forms in the Brain appeared first on University Health News.

Read Original Article: MGH Researchers Discover How Amyloid Beta Forms in the Brain »