Imaging Biomarkers: Challenges, Opportunities, and the Road Ahead

Over the last several years, significant advances in the Alzheimer’s disease (AD) research spectrum have presented clear opportunities in both the diagnosis and management of the disease. However, the path to realizing these potential benefits is littered with roadblocks. At the 2016 American Academy of Neurology Annual Meeting in Vancouver, Liana Apostolova, MD, Barbara and Peer Baekgaard Professor in Alzheimer’s Disease Research at Indiana University, directed a course on the current state of AD biomarkers. As part of Practical Neurology®’s video coverage of the meeting, Dr. Apostolova recapped key points from the course and shared insights on the rapidly evolving diagnostic and therapeutic landscape.

“Currently we have several biomarkers to use in the clinic for evaluating neurodegeneration,” Dr. Apostolova observed. “Those are Magnetic Resonance Imaging (MRI), computed tomography (CT) of the brain to look at atrophy, and fluorodeoxyglucose positron emission tomography (PET) to ascertain the presence of hypometabolic changes and rule out frontotemporal dementia,” she continued. “One biomarker that has generated a good deal of excitement but is still only available in research settings is tau PET imaging, which involves the injection of radioligand that is sensitive to the second protein that deposits in AD—the tau protein—that is associated with neurodegeneration and leads to neuronal demise, damage, death, and the cognitive decline that we observe readily,” said Dr. Apostolova. “That kind of technology is still in the research stages, although our ability to utilize it and understand what it all means has been improving with rapid speed, so it is the hope that we will have also tau imaging one day available for clinical use as an FDA approved and hopefully insurance covered imaging modality.”

The importance of such technology would be staging of AD, according to Dr. Apostolova. “As opposed to amyloid PET, which gives us information about whether AD plaques are present or absent in the brain without a strong relationship to how severely impaired the patient is, tau imaging will allow us to stage it,” That might translate to more personalized types of therapy. One day when we have disease modifying drugs available, we might be able to select the appropriate agent based on the stage the patient is in.”

Recent changes in the Alzheimer’s diagnostic criteria now enable physicians to use biomarkers to ascertain the presence of AD pathology in the brain. These criteria, according to Dr. Apostolova, “allow physicians to diagnose MCI due to AD and dementia due to AD based on positive amyloid biomarkers.” Unfortunately, while the new imaging technology could improve diagnostic accuracy and better allow physicians to counsel and treat patients, “Insurance is still lagging behind in providing coverage for this type of technology in the clinic,” lamented Dr. Apostolova.

With increased access to these tools, Dr. Apostolova believes that the benefits will stretch beyond Alzheimer’s detection and treatment. “It is not just about being able to identify cases that are experiencing cognitive decline due to AD; it is very much about making sure we don’t mistreat cases that are not due to AD,” she said. “We now know that about 50 percent of MCI cases and 30 percent of cases of AD dementia do not harbor the changes of Alzheimer’s pathology in the brain, meaning they have other causes of cognitive decline.” Identifying these patients is critical for the purposes of offering appropriate work-up and treatment and improving our understanding of what is not Alzheimer’s disease, Dr. Apostolova noted. n