For several years, a Blood test that can detect the presence of, or risk for, Alzheimer’s disease has been the “holy grail” for researchers.

Fortunately, such a test may be close to becoming a reality.

Researchers at Washington University of St. Louis (WUSTL) working in tandem with colleagues at the Center for Neurodegenerative Diseases in Germany think they have found the key: neurofilament light (NfL) chain, a protein that helps form the neurons (or nerve cells) in your Brain.

When neurons in the brain sustain damage and start to die, as they do in the beginning stages of Alzheimer’s disease, NfL first leaks into (and becomes detectable in) cerebrospinal fluid — the protective liquid that surrounds your brain and spinal cord — and eventually leaks into the blood.

In findings published on January 21, 2019, in the journal Nature Medicine, the WUSTL and German researchers demonstrated that elevated levels of NfL in the blood reflect neurological damage, not just in Alzheimer’s but in other neurodegenerative conditions, such as multiple sclerosis and stroke.

The results are significant because up until now, it was thought that only elevated levels of NfL in the cerebrospinal fluid were indicative of damage — and that testing for them required an expensive, invasive, and sometimes painful procedure called a spinal tap.

Neurofilament Light Chain Rise Not Specific to Alzheimer’s Disease

“Any disease that leads to damage in the brain will cause cerebrospinal fluid and blood levels of NfL to go up,” says Brian Gordon, PhD, study coauthor and assistant professor of radiology at WUSTL’s Hope Center for Neurological Disorders.

“The protein is highly sensitive to damage, but isn’t specific for any one disorder. Our current paper shows that blood-based measures of NfL strongly relate to these other neurodegenerative markers and also relate to changes in cognition,” Dr. Gordon says.

Unique Alzheimer’s Population Key to Blood Test Study

Gordon and his colleagues worked with more than 400 participants in the Dominantly Inherited Alzheimer’s Network (DIAN), an ongoing, international study looking into the genetic roots of Alzheimer’s. Of these participants, 247 were known to carry a rare genetic variant that is known to cause Alzheimer’s at a young age, while the remaining 162 were their unaffected relatives. All of the study participants had been asked to submit blood samples, undergo brain scans, and complete cognitive tests.

The researchers found that participants with the faulty gene variant had higher NfL levels at their initial examination than those without the variant, and that these levels continued to increase over time. In addition, those with the healthy form of the gene had low and stable NfL levels over time.

Furthermore, in 39 people with the faulty genetic variant, the researchers noted that those in whom NfL blood levels were found to have increased rapidly were more likely to show signs of brain atrophy and cognitive decline when they revisited the clinic.

Hopes That Blood Test Could Become Routine Neurological Tool

Based on these observations, Gordon believes future clinical trials for drugs designed to treat Alzheimer’s “could use a blood-based NfL test to see if [the drug] prevents or slows Alzheimer’s-related neurodegeneration.” He adds that, eventually, “blood-based measures could become a routine test” during a neurological exam.

“It could be a low-cost tool to help [neurologists] determine if there is some sort of active trauma occurring in the brain,” he notes.

This latter step, however, may be several years away from becoming reality, although commercial blood tests for Alzheimer’s are currently being evaluated.

Improvements in Blood-Analysis Equipment Credited With Rapid Advances

Still, those involved in advocacy and support for those with condition are excited by the Nature Medicine study findings. In fact, the Alzheimer’s Drug Discovery Foundation (ADDF) suggests such blood tests could become part of its Diagnostics Accelerator program, which was started last fall in partnership with philanthropist Bill Gates and foundation cofounder Leonard Lauder, to “develop novel biomarkers for the early detection of Alzheimer’s … and related dementias.”

“This study is evidence we can develop and will develop one or more blood tests for Alzheimer’s in the next two to four years,” notes Howard Fillit, MD, ADDF’s founding executive director and chief science officer, as well as a geriatrician and neuroscientist at Mount Sinai School of Medicine in New York City.

Dr. Fillit credits the development of highly sensitive blood-analysis equipment, which has evolved particularly rapidly over the past 25 years, with making such tests possible. And as exciting as a blood test for Alzheimer’s is for those who may be at risk for the condition, he sees their development as also marking a significant advance for researchers.

Lower-Cost Screening Tools Could Accelerate Alzheimer’s Research

Drug trials related to the neurological condition have historically been expensive, in large part because costly brain scans have been required to adequately screen study participants. As the findings of Gordon and colleagues demonstrate that blood NfL levels parallel Alzheimer’s progression as documented via brain scans, tests based on the protein could reduce costs for researchers and therefore accelerate drug development.

A key part of the ADDF’s Diagnostics Accelerator program will not only be supporting research into new approaches but also ensuring they get into the hands of physicians and, ultimately, become widely available for their patients.

“Just like the discovery of high cholesterol as a risk factor for heart disease revolutionized treatment of that condition, this will revolutionize both the diagnosis and treatment of Alzheimer’s,” he says.

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