Detecting a protein in the blood could track the progress of Alzheimer’s onset.
The protein is called neurofilament light. It spills out of damaged and dying nerve cells, into the cerebrospinal fluid and then travels from there into the bloodstream.
Previous studies have already demonstrated that blood levels of neurofilament light are higher in people with diseases, such as Alzheimer’s, that destroy nerve cells and tissue in the brain. However, few of these have been long-term investigations.
The new study, which features in JAMA Neurology, suggests that measuring blood levels of neurofilament light could indicate whether drugs for treating Alzheimer’s disease are working. As yet, there is no noninvasive way of doing this.
The findings follow those of another investigation that showed that measuring neurofilament light in the blood could identify Alzheimer’s disease 10 years or more before the emergence of symptoms such as decline in thinking and memory.
However, the earlier study was limited to identifying people with a rare, inherited, early-onset form of Alzheimer’s disease that usually strikes before the age of 65. The more recent research applies to sporadic Alzheimer’s disease, a far more common, late-onset type that most often strikes after the age of 65.
“Taken together,” says lead study author Dr. Niklas Mattsson, a physician at Skåne University Hospital who also does research at Lund University, both in Sweden, “these studies indicate that [neurofilament light] in the blood can be used to measure damage to brain cells in various forms of Alzheimer’s disease.”
Alzheimer’s disease and brain changes
The most common early symptom of Alzheimer’s disease is short-term memory loss, and this, together with other symptoms of cognitive and physical deterioration that result from loss of brain cells, gradually worsens over time. Eventually, the disease can stop people from being able to live independently, as they lose the ability to relate to others and their environment.
According to figures from the Alzheimer’s Association, there are 5.8 million people living with Alzheimer’s disease in the United States, and this number is likely to rise to just under 14 million by 2050.
There is currently no cure for Alzheimer’s disease. There are some treatments that can alleviate some of the symptoms for a little time, but none, as yet, can stop the disease from progressing.
The changes in the brain that accompany Alzheimer’s disease begin a long time before the early symptoms start to appear. These changes include the toxic buildup of tau and beta-amyloid proteins that damage nerve cells’ ability to communicate and function and eventually cause their death.
Blood test ‘cheaper and easier’
For their investigation, Dr. Mattsson and his colleagues used data from the Alzheimer’s Disease Neuroimaging Initiative, a multisite study that is evaluating imaging and other biomarkers for early detection and progress-monitoring of Alzheimer’s disease.
The data came from records of 1,583 individuals in North America who had given regular blood samples for up to 11 years during 2005–2016 and whose blood analysis included measures of neurofilament light.
Just over 45% of the cohort was female and the average age was 73 years. Of the individuals, 401 had no cognitive impairment, 855 had mild cognitive impairment, and 327 had dementia due to Alzheimer’s disease.
The researchers analyzed measures of neurofilament light protein together with other data that included: information from clinical diagnoses; markers of beta-amyloid and tau protein in cerebrospinal fluid; results from PET and MRI scans; and scores from thinking and memory tests.
Dr. Mattsson says that they found that levels of neurofilament light protein rose “over time in Alzheimer’s disease” and that they were “in line with the accumulated brain damage” that was reflected in the brain scans and cerebrospinal fluid markers.
“Standard methods for indicating nerve cell damage,” he explains, “involve measuring the patient’s level of certain substances, using a lumbar puncture, or examining a brain MRI.”
“These methods are complicated, take time, and are costly,” he continues, adding that “Measuring [neurofilament light] in the blood can be cheaper and is also easier for the patient.”
Potential for use in drug development
One application of such a test could be to find out if a drug is actually slowing or stopping the loss of nerve cells in the brain.
“Within drug development,” Dr. Mattsson comments, “it can be valuable to detect the effects of the trialed drug at an early stage and to be able to test on people who do not yet have full-blown Alzheimer’s.”
He emphasizes the need to continue studying neurofilament light as a potential biomarker for Alzheimer’s disease. For instance, questions remain about the marker’s sensitivity and how it changes in the long term. New studies also need to examine the effects that new drugs might have on levels of the protein.
In the meantime, he suggests that even with all this necessary work ahead, a blood test that uses neurofilament light might be here sooner than people might think.
For instance, he mentions that an ongoing project at Sahlgrenska University Hospital in Gothenburg, Sweden, aims to make such a test “available as a clinical procedure in the near future.”
“Physicians can then use the method to measure damage to nerve cells in Alzheimer’s disease and other brain disorders through a simple blood test.”
Dr. Niklas Mattsson