Dynamic Change of Neurofilament Light: Alzheimer's Diagnostic Progress

A simple blood test can reliably detect brain damage in people in the process of developing Alzheimer's disease, even before they show signs of confusion and memory loss, according to one new study from the Washington University School of Medicine in St. Louis and the German Center for Neurodegenerative Diseases in Germany.

The results, published on January 21 in Nature Medicine, could one day be used to quickly and inexpensively identify brain damage in people not only suffering from Alzheimer's disease but also other neurodegenerative diseases such as multiple sclerosis, traumatic brain injury or stroke. .

"This is something that would be easy to incorporate into a screening test at a neurology clinic," said Brian Gordon, PhD, badistant professor of radiology at the Mallinckrodt Institute of Radiology at the University of Washington and author of the study. "We have validated it in people with Alzheimer's disease because we know that their brain is undergoing significant neurodegeneration, but this marker is not specific to Alzheimer's disease. High levels could be a sign of many neurological diseases and injuries. "

The test detects the light chain of the neurofilament, a structural protein that is part of the inner skeleton of neurons. When brain neurons are damaged or dying, the protein escapes into the cerebrospinal fluid that bathes the brain and spinal cord and then into the bloodstream.

The discovery of high levels of protein in a person's cerebrospinal fluid has been shown to be strong evidence that some of his brain cells have been damaged. But getting cerebrospinal fluid requires a spinal tap, which many people are reluctant to undergo. Lead author Mathias Jucker, PhD, professor of cellular neurology at the German Center for Neurodegenerative Diseases in Tübingen, as well as Gordon and colleagues from around the world, investigated whether protein levels in the blood also reflected neurological damage .

They turned to a group of families with rare genetic variants responsible for Alzheimer's disease at a young age, usually in their fifties, forties, and even in their thirties. Families are the study population of the hereditary-dominated Alzheimer's network (DIAN), an international consortium led by the University of Washington that studies the roots of Alzheimer's disease. A parent carrying such a mutation has a 50% chance of pbading genetic error to a child, and any child who inherits a variant is almost badured of developing dementia symptoms of the same age than his parent. This timeline gives researchers an opportunity to study what is happening in the brain in the years preceding the onset of cognitive symptoms.

The researchers studied more than 400 people participating in the DIAN study, including 247 carriers of an early-onset genetic variant and 162 of their unaffected relatives. Each participant had already visited a DIAN clinic to donate blood, brain tests and cognitive tests. About half had been evaluated more than once, usually two or three years apart.

In patients with the defective genetic variant, protein levels were higher initially and increased over time. In contrast, protein levels were low and largely stable in individuals with the healthy form of the gene. This difference was detectable 16 years before the probable appearance of cognitive symptoms.

In addition, when the researchers examined participants' brain scans, they found that the rate of rise in protein levels was a function of the rate at which the precuneus – a part of the brain involved in memory – had been reduced and Shrunk.

"Sixteen years before the onset of symptoms, it's really early enough in the process of the disease, but we could see differences even then," said Stephanie Schultz, a student of postgraduate at the University of Washington, one of the co-first authors of the article. "This could be a good preclinical biomarker to identify those who will develop clinical symptoms."

To find out whether blood protein levels could be used to predict cognitive decline, researchers collected data on 39 individuals with disease-modifying variants when they returned to the clinic two years on average after their last visit. . Participants underwent brain exams and two cognitive tests: the mini-mental state exam and the logical memory test. The researchers found that people whose blood protein levels had increased rapidly before were more likely to show signs of brain atrophy and decreased cognitive abilities when they returned to the clinic.

"It will be important to confirm our findings regarding late-onset Alzheimer's disease and to define the period during which neurofilament changes should be evaluated in order to optimize clinical predictability," he said. said Jucker, head of the DIAN study in Germany.

All kinds of neurological damage can cause the neurofilament's light protein to spill out of the neurons in the blood. Protein levels are high in people with Lewy body dementia and Huntington's disease; they occur dramatically in people with multiple sclerosis during a push and in football players immediately after a blow to the head.

A commercial kit – very similar to the one used by the authors – is available to test protein levels in the blood, but it has not been approved by the FDA to diagnose or predict the risk of an individual's brain injury. Before being able to use such a test for patients with Alzheimer's disease or any other neurodegenerative disorder, researchers will need to determine how much protein in the blood is too much and how quickly protein levels can increase. before becoming a subject of concern.

"I could see that this would be used at the clinic in a few years to identify the signs of brain injury in individual patients," said Gordon, who is also an badistant professor in psychological and brain sciences. "We are not up to the point of telling people," In five years, you will suffer from dementia. "We are all working in this direction."

This article has been republished from documents provided by the Washington University School of Medicine in St. Louis. Note: Content may have changed for length and content. For more information, please contact the cited source.

Reference:

Preische, O., Schultz, S.A., Apel, A., Kuhle, J., Kaeser, S.A., Barro, C.,. . . Jucker, M. (2019). The dynamics of serum neurofilaments predicts the neurodegeneration and clinical progression of presymptomatic Alzheimer's disease. Nature Medicine. doi: 10.1038 / s41591-018-0304-3