What happens to the brain, at different stages of Alzheimer’s disease, remains a mystery, and new data from a team of doctors, scientists and technicians at Johns Hopkins University and the Johns Hopkins Nanoscience Laboratories may provide key clues.
A report published Monday in the journal Nature Medicine details findings about a groundbreaking experiment in which real-time imaging of the brain simultaneously catalogs what happens at different stages in cognitive decline.
It is the first time that brain-imaging methods have been used to follow how Alzheimer’s disease progresses in real time and even reveal potential prognoses for its progression. In this case, researchers were able to use PET scans of the brain, a tool that uses heat from an energy source to examine chemicals and proteins in the tissue of the brain. By exposing the brain to that heat, they were able to see what was happening at specific stages of disease progression.
Using real-time brain imaging, the researchers were able to show that what’s known as the hippocampus — which is critical for learning and memory — shrank for more than two years in mice, over a period of six months. The hippocampus is part of the hippocampus region of the brain that processes information relevant to other brain regions such as the cortex.
In people, memory and Alzheimer’s disease are often related, although the brains of people who develop the disease may be different in other ways, including the hippocampus.
The research does not prove cause and effect, but the researchers say it did show the procedure allowed them to track the disease from the outset. “What we are saying is this data is not going to sit on the shelf,” said James Joseph, professor of psychiatry and behavioral sciences at Johns Hopkins University and lead investigator of the study.
“If it is really important that we know how Alzheimer’s disease progresses, this is an important study that will be valuable,” said Alan Miner, director of the Alzheimer’s Disease Research Center at the Cleveland Clinic. “This is the future — it’s the first of many.”
Researchers found there is a progression of decline in brain function and gray matter areas as the disease progresses.
Miner, Joseph and others in the field were first able to learn that Alzheimer’s disease progresses differently in different brain regions using PET imaging and the PET brain-scanning tool that Johns Hopkins developed. Their work prompted the creation of a major consortium called the 24 Hour Neuroimaging Initiative — a network of 40 centers — to study the progression of disease in real time. They published a study in 2012 that showed a statistically significant pattern of decline over time.
In a current research project, known as the Alzheimer’s Disease Neuroimaging Initiative, researchers are using a more sensitive scanning method that does not reveal the brain’s physical structure, which can serve as evidence of biological changes. It is the most sophisticated way to examine neurological disease and was made possible by funding by the National Institutes of Health.
“All of our work since that paper was done primarily on dogs and cats that are normal and have a similar age to people with Alzheimer’s disease,” Joseph said. “What we can do here is apply this approach to humans.”
Using PET imaging, which is not yet FDA-approved for medical uses, researchers can see the degeneration of brain tissue, hear what’s happening in the brain at different stages of disease and see whether there are any changes in the brain that would suggest new diagnoses, Joseph said. “Using this technique, we can see changes in human brains as much as 3½ years after a diagnosis,” he said.
Based on the feedback of medical experts, the next goal in the research is to develop ways to move the findings from PET imaging to clinical use, Joseph said.
“Our hope is to really use it to see the disease take root and further differentiate between the different centers of the brain that respond differently,” Joseph said.