A compelling new study from an international team of researchers has described a novel protein that could be a useful blood-based biomarker to monitor the progression of Alzheimer's disease over a decade before any clinical symptoms appear.
Many researchers around the globe are on the hunt for effective ways to identify Alzheimer's before signs of cognitive decline appear. It is thought the disease can take 10 to 20 years of slow, quiet neurodegeneration before clinical symptoms appear, and it is during this time that many preventative treatments could be the most effective.
A variety of blood tests are currently in development, tracking everything from toxic amyloid proteins to autoantibodies that signal the presence of neurodegeneration. This new prospective blood test looks at a different blood-based protein biomarker called neurofilament light (NfL), which is released into a person's bloodstream as a consequence of brain cell damage.
"Normally, however, such proteins are rapidly degraded in the blood and are therefore not very suitable as markers for a neurodegenerative disease," explains Mathias Jucker, one of the head researchers on the new study. "An exception, however, is a small piece of so-called neurofilament that is surprisingly resistant to this degradation."
In order to study the correlation between NfL blood levels and the onset of Alzheimer's, the researchers examined data from 405 subjects involved with the Dominantly Inherited Alzheimer Network (DIAN), a long-term research network that follows families with inherited Alzheimer's disease. The study revealed a clear correlation between rising NfL levels and the onset of clinical Alzheimer's symptoms.
"The blood test accurately predicted when members of a family with inherited Alzheimer's disease would begin to show symptoms," says Colin Masters, a researcher working on the project from the Florey Institute. "Inherited Alzheimer's is [a] rare genetic disease. Using this very defined patient population we were able to identify affected family members over a decade before they began to show cognitive impairments."
Interestingly, the study suggests that there isn't an absolute NfL level that can point to the onset of Alzheimer's, but instead the key metric seems to be an increasing rate of change. So, rather than NfL levels working as a one-off diagnostic blood test, it may only be useful as a biomarker tracked over several years of blood testing.
"It is not the absolute neurofilament concentration, but its temporal evolution, which is meaningful and allows predictions about the future progression of the disease," says Jucker.
The study has several limitations that will require further work before the blood test can be widely implemented. These initial results are only relevant to patients with a very rare genetic familial risk of developing Alzheimer's, and not the more common form of the condition, often referred to as sporadic Alzheimer's disease.
The researchers do suggest that familial and sporadic Alzheimer's disease share fundamental pathophysiology and progression, so NfL levels should function as an effective biomarker in both instances, but further study will be needed to tease this correlation out. The other problem is that NfL levels can be influenced by other age-related neurodegenerative conditions, suggesting it may not be as useful for older patients as it would be for younger patients at risk of early-onset dementia.
All of these concerns will clearly be the source of much follow-up work, so it may be some time before this type of testing is widely implemented. However, the researchers are hopeful this could be a simple addition to the standard assortment of GP tests we undergo as we get older. Any unusual spike in NfL levels may allow doctors to better identify patients in need of closer examination for early-onset cognitive decline.
The new study was published in the journal Nature Medicine.
Sources: German Center for Neurodegenerative Diseases, SciMex
