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    Mayo study differentiates what blood-based proteins indicate about brain cell loss

Human brain research and memory loss as symbol of alzheimer's concept with missing pieces of the puzzle

ROCHESTER, Minn. — Two proteins that can be measured in the blood — plasma total tau and neurofilament light — are associated with brain cell loss that causes memory and thinking problems. Neurofilament light was more strongly related to worse cognition and neurodegeneration, compared to total tau, according to a preliminary Mayo Clinic study that will be presented in the Emerging Science program at the 2021 virtual American Academy of Neurology Annual Meeting.

Brain cell loss, or neurodegeneration, is a common characteristic of many disorders, including Alzheimer's disease, vascular dementia and Lewy body dementia. However, the causes and location of neurodegeneration in the brain vary depending on the disease.

"Understanding which marker is associated with which aspect of neurodegeneration will inform how each marker can best be used for specific clinical purposes and what information each marker provides," says Michelle Mielke, Ph.D., a Mayo Clinic epidemiologist and neuroscientist, and senior author of the study.

In the study, 995 participants enrolled in the community-based Mayo Clinic Study of Aging had data collected for plasma neurofilament light, total tau, cognitive status and neuroimaging. Follow-up tests were repeated about every 15 months for a median of more than six years.

The findings showed that, at baseline, neurofilament light was more strongly associated with brain atrophy in multiple areas and brain white matter changes, as well as changes to global cognition — memory, attention, verbal fluency, language, and the ability to understand images and interpret spatial relationships.

However, the combination of having elevated neurofilament light and total tau were more strongly associated with worse memory performance and cognition than each biomarker individually. Thus, as a diagnostic tool, it may be useful to add measurement of total tau to neurofilament light, Dr. Mielke notes.

For prognosis purposes, these findings also show that neurofilament light better predicts the rate of neurodegeneration and cognitive decline, regardless of what the cause of neurodegeneration might be. Therefore, neurofilament light may help determine how fast someone declines and how effective future therapies might be in slowing this decline.

Watch: Michelle Mielke, Ph.D., participating in the 2021 AAN Annual Meeting Top Science Press Conference

Note: Dr. Mielke begins speaking at 35:23.

Results from the Mayo Clinic Study of Aging cohort were replicated in the multicenter Alzheimer's Disease Neuroimaging Initiative cohort, suggesting the findings can be replicated across clinical settings.

Researchers involved in this study were Jordan Marks; Jeremy Syrjanen; Jonathan Graff-Radford, M.D.; Ronald Petersen, M.D., Ph.D.; Mary Machulda, Ph.D.; Michelle R. Campbell; Alicia Algeciras-Schimnich, Ph.D.; David Knopman, M.D.; Clifford Jack Jr., M.D.; and Prashanthi Vemuri, Ph.D. ― all of Mayo Clinic.

This research was funded by National Institutes of Health and National Institute on Aging grants, the GHR Foundation, and the Rochester Epidemiology Project.


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