NfL is not specific for any one condition, but it could be “valuable as a relatively inexpensive and fast test for accumulating neurodegeneration in the brain” when used in the clinic and in clinical trials, said study investigator Abdul Hye, PhD, of the Institute of Psychiatry, Psychology and Neuroscience, King’s College London, United Kingdom.
NfL is a structural protein that forms the internal skeleton of neurons. When neurons are damaged, NfL is released into cerebrospinal fluid and blood. It is currently being studied as a potential biomarker for many different neurologic diseases.
NfL is an “excellent axonal injury biomarker,” Hye told the briefing. Differences in NfL levels in blood between healthy people and patients with neurodegenerative diseases are widely accepted, but less is known about how plasma concentrations of NfL differ across neurodegenerative disorders, he explained.
To investigate whether NfL is a “cross neurodegenerative” blood-based biomarker, the researchers compared plasma NfL concentrations across multiple neurodegenerative and neurologic conditions in more than 2300 individuals from two cohorts.
Conditions included mild cognitive impairment (MCI), Alzheimer disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), Parkinson disease (PD), and primary tauopathies. Several other conditions, such as vascular dementia, Down syndrome (DS), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and clinical depression, were also included. Healthy control persons were also included.
Both cohorts showed similar increases in NfL across multiple neurodegenerative conditions, said Hye.
The lowest average NfL concentrations were found in control persons and clinically depressed individuals (30 and 11 pg/mL, respectively). The highest plasma NfL concentrations were found in patients with ALS (143.9 pg/mL), DS-D (80 pg/mL), and DLB (79.6 pg/mL). Compared with control persons, statistically significant differences in plasma NfL concentrations were observed for patients with FTD, corticobasal syndrome (CBS), DS-D, DLB, and ALS.
Using a plasma NfL concentration cutoff of 44.7 pg/mL, abnormal levels predicted more than 80% of cases of ALS, 100% of cases DS-D, 60% of cases of CBS, and more than 50% of FTD cases. NfL levels were abnormal in only 2% of healthy control persons, a finding that strengthened the choice of cutoff point, the researchers say.
However, in both cohorts, NfL concentrations were abnormal in only 20% to 30% of those with AD, “which is not the best,” Hye told the briefing. The researchers replicated this finding using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).
Reached for comment, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer‘s Drug Discovery Foundation, told Medscape Medical News, “What we are seeing with NfL in the blood is that it kind of predicts who is having active neurodegeneration but isn’t clinically really sick yet.
“NfL in the blood is a sign of axonal damage in the brain, but it’s not specific to any one neurodegenerative disease, like Alzheimer‘s disease. But it still could have a role in the diagnostic algorithm,” said Fillit.
Bruce Lamb, PhD, vice chair of the Alzheimer‘s Association Medical and Scientific Advisory Group, who moderated the press briefing at AAIC 2019, where the results were presented, said that currently, there is a “global race to uncover and develop blood-based biomarkers of Alzheimer‘s disease and other dementias.”
Blood-based biomarkers will be “essential and would be welcome by clinicians, researchers, and the public because in general, they are cheaper, easier to administer, less invasive, and more accessible than all other technologies currently available. The hope is that we can develop these as early detection tools and use them to track the impact of therapeutic interventions,” said Lamb.
“While these tests are not quite ready for prime time, we are actually much closer than I think we even thought we would be just a few years ago,” said Lamb.
Funding for the study was provided by the National Institute for Health Research, the European Research Council, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Marianne and Marcus Wallenberg Foundation, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, the Parkinson Foundation of Sweden, the Skåne University Hospital Foundation, and the Swedish federal government. Hye, Lamb, and Fillit have disclosed no relevant financial relationships.
Alzheimer‘s Association International Conference (AAIC) 2019: Abstract P2-618. Presented July 15, 2019.