Study: Test could detect Alzheimer's years before symptoms begin

Blood test IDs disease 16 years before symptoms

By NINA AVRAMOVA, CNN
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(CNN) - A simple blood test could predict if a patient will develop Alzheimer's disease up to 16 years before symptoms begin, a new study finds.

By measuring changes in the levels of a protein in the blood, called neurofilament light chain (NfL), researchers believe any rise in levels of the protein could be an early sign of the disease, according to the study published Monday in the journal Nature Medicine.

NfL is a "marker in the blood which gives an indication of nerve cell loss in the brain," explained lead researcher Mathias Jucker, professor of cell biology of neurological diseases at the German Center for Neurodegenerative Diseases. ''The more neurofilament you have in the blood, the more brain damage you have," he said.

There is still no effective treatment for Alzheimer's, but Jucker thinks the new blood test will be "very important for clinical studies." He hopes the test will allow researchers to monitor the effectiveness of new treatments before people have started to experience symptoms, by measuring how levels of the protein are affected.

"Alzheimer's disease starts at least a decade, maybe even 20 years, before we have any symptoms," said Jucker, who is also board director at the Hertie Institute for Clinical Brain Research at the University of Tübingen.

There is currently no test doctors can use to conclusively determine whether someone will get Alzheimer's disease and there are a lot of unknowns about its cause. One widely believed theory is that the disease is driven by the production and deposition of beta-amyloid plaques between neurons in the brain.

In the UK, there are 850,000 people living with dementia, Alzheimer's disease is the most common type of this condition, according to the Alzheimer's Society in the UK. According to the US Centers for Disease Control and Prevention, as many as 5 million Americans have Alzheimer's disease.

Of the many changes in the brain which precede the disease's symptoms, one change is also the accumulation of NfL in the blood before any symptoms begin, said Jucker.

Jucker's team measured the rate of change in NfL using a blood test in 405 individuals from across the world enrolled in the Dominantly Inherited Alzheimer's Network -- an international research effort focused on dominantly inherited Alzheimer's disease, a rare form of the illness that represents less than 1% of all cases of Alzheimer's, according to the National Institute on Aging.

The team measured NfL protein levels in the participants through blood samples, brain imaging and cognitive tests on average every two and half years over the last seven years. The study is ongoing.

The patients carrying the gene mutations predisposing them to Alzheimer's disease -- a group of 243 -- were found to have increasing levels of NfL compared to the control group, consisting of 162 family members without the mutation.

By measuring the protein, Jucker said "we can measure with our blood test the changes in the brain many, many years before we have the symptoms." So far, 13 participants had developed Alzheimer's.

Through the cognitive testing and brain imaging, NfL levels were shown to be correlated with cognitive decline and brain shrinkage, said Jucker. Researchers also found an association between 39 participants' changing NfL levels and brain loss and cognitive decline after two years.

The findings come together to show that changes in NfL levels were an accurate predictor of how brain damage develops, according to the study.

Jucker likened his team's work to the cancer field. "In general this is not something new," he explained, as certain markers, for example, tell people they have cancer even when there are no symptoms of the disease. The test is already commercially available; it detects NfL in cerebrospinal fluid for measurement of different neurological conditions, and Jucker is confident that future clinical trials for new Alzheimer's drugs will include the marker his team developed.

But Jucker warns that the test is not specific to Alzheimer's disease, he added. Higher levels of neurofilament indicate brain damage, but this can also be due to brain injury from an accident, for example.

This is not the first blood test developed in hope of diagnosing the disease early.

Previous research has shown options for detecting Alzheimer's disease in its early stages. A 2018 study examined the presence and levels of amyloid beta in a person's brain by looking at people with varying levels of health, including some with who were healthy, some who had mild cognitive impairments and some who had Alzheimer's disease.

In 2014, using a blood test that looked at 10 specific lipids in people's blood, researchers were also able to predict Alzheimer's before symptoms appeared.

James Pickett, head of research at the UK's Alzheimer's Society pointed out that the study's participants had a faulty gene "which causes an inherited form of the disease."

Pickett, who was not involved in the study, said in an email to CNN that "from these results it looks like regular blood tests in this group of patients could replace doing more invasive spinal taps, but would still need to happen alongside other tests like brain scans and memory tests to rule out other causes."

Sarah Marzi, a postdoctoral researcher at Queen Mary University of London, said that the researchers "most promisingly" show changes of NfL predicting cognitive test results and thinning of the cortex, "two main symptoms of Alzheimer's Disease."

Marzi, who was not involved in the research, said in an email to CNN that if "this result can be replicated in larger cohorts and more generally in sporadic cases of Alzheimer's Disease, the blood test for NfL would indeed be a promising biomarker or diagnostic tool."

"However, so far the authors have only shown this in a small sample (39 individuals) of people who all carried Alzheimer's Disease risk mutations."

Dr. Charles Marshall, clinical lecturer in neurology at Queen Mary University of London, said in an email to CNN: "This is exciting because it might allow treatments to be started early, and therefore prevent the development of dementia."

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