MUSC studies explore impact of Alzheimers on brain

Neuroscience researcher Jane Joseph wants to find a way to fight the disease that killed her father. “My dad had Alzheimer’s, and he passed away two years ago. You always feel helpless when there’s a disease that doesn’t have a treatment. This is kind of my way of feeling like I can do something about it.”

Alzheimer’s disease has been studied for more than a century, and there is still no cure, although the condition affects more than 5 million Americans. There are medications that can help with the symptoms but nothing that gets at the disease itself.

Joseph is one of three Medical University of South Carolina brain researchers trying to change that with the help of recent grants from the National Institutes of Health, totaling more than $7 million.

Using connectomics to characterize risk for Alzheimer's disease

Joseph, a professor in the MUSC College of Medicine, is working with clinical researcher Jacobo Mintzer on a study called “Using connectomics to characterize risk for Alzheimer’s disease.” Connectomics involves creating maps of connections within the brain using technology.

“The overall goal is to use neuroimaging, in particular MRI, to really come up with a biomarker or biomarkers to predict someone’s risk for Alzheimer’s disease,” Joseph said. MRI stands for magnetic resonance imaging.

“If you know a person’s risk for Alzheimer’s, you may be able to take measures to try to at least slow the progression of the disease or make lifestyle adjustments to make the onset easier to cope with.”

The study involves the use of a technique called functional connectivity. “It basically characterizes the networks of the brain, how the different regions communicate with and influence each other and how they might activate together in different situations,” Joseph said.

Mintzer put it this way. “We want to understand the main streets affected in Alzheimer’s disease, so we can find ways to develop alternative pathways that will allow the information to flow better.”

He and Joseph will recruit volunteers who have Alzheimer’s disease and create maps of their brains. Joseph said the type of imaging they will use is relatively non-invasive. “It’s kind of easy to look into the brain of Alzheimer’s disease. In my mind, it’s a relatively low-risk way we can start to chip away at the problem and figure out what’s really going on, at least in terms of how the brain communicates, how the different regions act together.”

That will give them what she calls a snapshot of the disease. “And then what we’re going to do is see if that network profile in Alzheimer’s is present in another group of subjects who are very much at risk, and that is people with mild cognitive impairment. It’s a way to begin to think about risk or quantifying someone’s risk for Alzheimer’s. Then we’re going to take that network profile and look at healthy aging subjects to see if any of those people show some of the pieces of the network degradation we’d see in Alzheimer’s disease.”

Joseph says when one part of a brain network deteriorates due to Alzheimer’s, other areas may try to compensate. That’s part of what the researchers hope to find out.

Their study, which will get $3,714,957 in funding over the course of five years from the NIH, will also use genotyping to try to create a profile of a person’s genetic risk of developing Alzheimer’s disease.

Quantitative neuroimaging assessment of white matter integrity in the context of aging and Alzheimer's disease

The other study, “Quantitative neuroimaging assessment of white matter integrity in the context of aging and Alzheimer’s disease,” will look at how the wiring in the brain changes over time. Joseph Helpern, a physicist known for his research in the area of MRI, is conducting this research with Mintzer. Mintzer is a medical doctor specializing in geriatric psychiatry.

Helpern described how the study will work. “Our volunteers will have two study visits about two years apart, where we’ll test mental function using neuropsychological testing and questionnaires and they’ll  undergo a brain MRI. At the first visit only, they’ll also have some blood drawn and get a PET scan.” PET, an imaging test that shows how the brain’s metabolism is working, stands for positron emission tomography.

Using advanced MRI techniques developed in Helpern’s lab, the researchers will be looking at myelin in the brain. Myelin is a fatty covering that protects nerve fibers called axons. Myelinated axons are white, so myelin is known as the white matter of the brain.

“We’re going to recruit 350 people between the ages of 45 and 85, get a baseline measure and follow them over time to see if our imaging methodology can be used to help differentiate those who are going to go on and get Alzheimer’s disease. We’ll measure the density and permeability of the axons, giving the first signs of breakdown of structural integrity.”

This advanced imaging technique uses water in the brain as a messenger. “Measuring how water moves in a normal elderly brain — which direction it goes, where and what it bumps into — can help us understand what is going on when it isn’t moving normally, say in a diseased brain. In other words, if we know how the water moves in the brain normally, we should be able to tell when it’s moving abnormally say in the early stages of developing A.D.,” Helpern said.

Mintzer said it may allow doctors to spot, very early, lesions that are linked with part of Alzheimer’s disease. “Today, doctors are tackling Alzheimer’s disease too late,” Mintzer said. “Dr. Helpern’s approach suggests we could learn at the very, very early stage of the disease that it’s developing. And maybe, if we are correct, we will understand ways that will allow us to take care of the disease in very different ways than we do today.”

The study will get of $3,729,934 in funding from the NIH over five years. Mintzer, a professor at MUSC, executive director of clinical research at the Alzheimer’s Research Center at the Roper St. Francis Clinical Biotechnology Research Institute, also treats patients at the Ralph H. Johnson VA Medical Center. He emphasized the importance of collaboration as scientists seek to finally find a cure for Alzheimer’s disease.

Both grants will bring together experts from MUSC, the Roper Alzheimer's Center and the Ralph H. Johnson VA Medical Center. But Mintzer is calling for more than collaboration among scientists.

“We need the whole community to be engaged. Through the months to come, we will be asking people to volunteer for research,” Mintzer said.