Are Better Biomarkers Necessary in Diagnosing Alzheimer’s Disease?

Friday, Dec. 04, 2020

By Richard Dargan

Two established imaging biomarkers have the potential to diagnose and predict the course of Alzheimer’s disease (AD) even before symptoms appear, according to one expert who spoke at RSNA 2020.

A second expert, however, argued that more and better biomarkers are needed to fully profile the disease.



Diagnosis of AD, the most common type of dementia, was previously possible only through post-mortem examination of the brain. Through advances in molecular imaging, it is now possible to identify in living people two abnormal brain deposits linked with the disease: amyloid plaques, hard, insoluble clusters of beta amyloid proteins, and neurofibrillary tangles, twisted fibers consisting primarily of a protein called tau. Both can be estimated with PET and cerebrospinal fluid (CSF) assays.

PET and CSF biomarkers of AD have potential for defining and staging the disease, an important capability considering that Alzheimer’s has a prolonged pre-symptomatic phase of 20 years or more.

“We want to know how early we can detect this disease and what may prolong this pre-symptomatic stage or accelerate conversion to symptoms,” said Sterling Johnson, PhD, professor at the University of Wisconsin School of Medicine and Public Health. “We’ve gained a great deal of clarity in this area thanks to PET and CSF biomarkers that are appropriate for Alzheimer’s disease.”

During the session, Dr. Johnson made the case for applications of amyloid and tau PET in exploring preclinical AD. Research he shared from the Wisconsin Registry for Alzheimer’s Prevention (WRAP), one of the world’s largest and longest-running studies of individuals at risk for the disease, showed that both the age of onset and chronicity, or years with amyloid positivity, can be estimated.

“Knowing the patient’s age when he or she became amyloid positive and knowing their current age, we can estimate how long the person has been living with this disease, even in the pre-symptomatic stage,” Dr. Johnson said. “This is going to give us tools to determine what is slowing this disease down.”

Better Biomarkers Necessary

As research around amyloid and tau intensifies, one expert called for the development of better biomarkers to profile the decline in AD and related disorders.



Steven E. Arnold, MD, translational neurology head of the Interdisciplinary Brain Center, Massachusetts General Hospital, Harvard Medical School, noted that patients with resilient Alzheimer’s pathology have high levels of disease pathology but good cognition.

“This tells us that while Alzheimer’s disease pathology may be necessary for a diagnosis of Alzheimer’s disease, it in and of itself is insufficient to cause mild cognitive impairment or dementia,” Dr. Arnold said. “Something else must be going on as well to cause cognitive impairment.”

Dr. Arnold identified several promising molecular biomarkers including proteins and non-disease-specific markers of neurodegeneration. His research team is working to identify spinal fluid or plasma profiles that predict the course of disease.

“Based on these profiles, we hope to create personalized profiles across different domains beyond amyloid and tau, spanning other misfolded proteins and inflammatory, metabolic, vascular injury and other domains,” he said.

“We have the hope that we can predict prognosis and also identify the most active drivers of nerve degeneration within an individual and hopefully target those therapeutically,” Dr. Arnold added.

After the presentation, Ciprian Catana, MD, PhD, associate professor of radiology at Harvard Medical School in Boston, moderated a question-and-answer session. Several attendees asked what can be done to delay the onset of dementia. Both presenters agreed that good health habits and regular intellectual stimulation are promising hedges against cognitive decline.

"If we can keep our brain healthier for longer, even if one has the proteinopathy that is Alzheimer's disease, it might be possible to prolong that state of being cognitively unimpaired," Dr. Johnson said.

"It's just common sense that good lifestyle practices and good health are going to sustain your brain in the same way that they sustain your heart," Dr. Arnold added.

For More Information:

View the Hot Topic Session, Integration of Novel Blood, CSF and Imaging Biomarkers for the Early Diagnosis of Alzheimer's Disease — SPSH52 at