Tracing the disease path: new insights into detection methods for Alzheimer’s disease

February 02, 2021
Brain tissue showing a flame-shaped neurofibrillary tangle in the center
Tau tangle (flame-shaped black structure at center) in the brain of a person with Alzheimer's disease. Image courtesy of Dr. Steven Carroll.

MUSC and Clemson researchers report in a recent article in Molecular Neurodegeneration that tracers can accurately track the amyloid plaques and tau tangles characteristic of Alzheimer’s disease (AD) in the autopsied brain tissue of people with Down syndrome and AD, early-onset AD and late-onset AD. Tracers are tiny amounts of a chemical that stick to specific proteins in tissue so that they can be visualized via a scan. These tracers concentrate in regions of the brain with amyloid and tau, providing a means to detect AD early and monitor its progression.

"By measuring the efficacy of reported tracers for these pathological symptoms, we come closer to a way of identifying at-risk individuals before signs of mental degeneration are apparent.”

Dr. Steven Carroll

Alzheimer’s disease is a devastating dementia characterized by progressive destruction of brain tissue and subsequent memory loss. While the causes of AD are still not well-understood, it is known that 80% of people with Down syndrome will develop AD by the age of 50. Indeed, autopsies reveal that the brains of nearly all people with Down syndrome older than 35 have the amyloid plaques and tau tangles characteristic of AD. Studies have shown that mental degeneration becomes more severe as the number of plaques and tangles grows.

While there is no cure for AD, therapies have been developed to slow the progression of the disease. However, these therapies are potentially most effective early in the disease, before severe damage has taken place. It is the goal of current research to develop new methods to detect AD early. Developing tracers to recognize and visualize tau and amyloid in the brain could help to determine risk for dementia later in life.

“Up until very recently, the only way to diagnose Alzheimer’s or another neurodegenerative disease was through an autopsy,” said Steven Carroll, M.D., Ph.D., chair of the Department of Pathology and Laboratory Medicine at MUSC. “By measuring the efficacy of reported tracers for these pathological symptoms, we come closer to a way of identifying at-risk individuals before signs of mental degeneration are apparent.”

Dr. Steven Carroll with a trainee 
Dr. Steven Carroll with a trainee, Photograph by Sarah Pack.

The researchers showed that the tracers for the proteins were just as accurate as traditional post-mortem detection methods for AD. They could also indicate the regions of the brain in which these proteins collect. The tracers could be useful for monitoring the progression of AD, especially in patients with Down syndrome in which the clinical signs are well established. 

Interestingly, the tracers also localized to different regions of the brain in people with Down syndrome and AD, late-onset AD and early-onset AD. Identifying which parts of the brain are involved in the progression of AD and how different dementias can progress will be critical to understanding the disease as a whole. It will also better enable clinicians to identify those who are at risk.

While the current tracers are an excellent way to detect the progression of AD, the test is expensive and time-consuming, according to Carroll. A cheaper blood-based test would allow for routine screening, which would lead to earlier, life-changing treatment for people with AD.

 “What I would like to see developed is a two-tier testing system in which a blood-based test can be used to identify early markers for Alzheimer’s,” said Carroll. “It could then be followed up with an accurate radiotracer test.”

Amyloid plaques in the brain of a person with Alzheimer's disease 
Amyloid plaques in brain of a person with Alzheimer's. Image courtesy of Dr. Steven Duncan.

Carroll is committed to establishing MUSC as an Alzheimer’s research center because South Carolina has a heavy burden of the disease.

 To understand more fully why dementia is common in South Carolina, Carroll and his team will need more people with the disease to be willing to sign on as organ donors for MUSC’s brain bank.

“South Carolina is hit hard by cases of dementia,” said Carroll. “I feel that we really need to pay more attention to this disease in this state.”

About the Author

Caleb Stratton
Caleb Stratton is a structural biologist currently studying resistance mechanisms in antibiotic- resistant bacteria in Dr. Christopher Davies’ lab. His interests are new discoveries in science and ethical dilemmas with new technologies.

Keywords: Research