Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Plasma levels of neurofilament light track neurodegeneration in MCI and Alzheimer’s disease

Key clinical point: Increases in plasma neurofilament light appear to track physical and cognitive changes as dementia progresses.

Major finding: Longitudinal plasma neurofilament light increased in association with several baseline and longitudinal hallmarks of Alzheimer’s disease.

Study details: The study comprised 1,583 subjects enrolled in the multicenter Alzheimer’s Disease Neuromaging Initiative.

Disclosures: Dr Mattsson reported being a consultant for the Alzheimer’s Disease Neuroimaging Initiative.


Mattsson N et al. JAMA Neurol. 2019 Apr 22. doi: 10.1001/jamaneurol.2019.0765.


This is an impressive study that convincingly demonstrates the sensitivity of plasma neurofilament light (NfL) to disease progression in patients with mild cognitive impairment and dementia in the Alzheimer’s Disease Neuroimaging Initiative cohort.

It is known that NfL is sensitive to neuronal damage that can result from a variety of pathologies, not limited to Alzheimer’s disease, so it is not diagnostically specific. In the present study there was even overlap of values between the cognitively unimpaired and mild cognitive impairment groups at baseline as well, although the levels separated over time.

In the right setting, NfL might still be a clinically useful diagnostic marker, especially for mild-stage disease when other clinical measures such as mental status scores and structural brain scans are inconclusive, and further study seems warranted for such a possibility.

Its greatest utility, however, will likely be in clinical trials. It would have been of the greatest interest to know how NfL levels changed in the setting of demonstrated cerebral amyloid clearance by agents such as aducanumab that failed to halt dementia progression, or in the setting of BACE1 inhibitor-related worsening of cognition. Did NfL levels remain static in the former and rise in the latter? Looking ahead, it seems likely that this easily accessed biomarker will become an integral part of clinical trial design. Assuming cost is not overly burdensome, it may even find its way eventually into clinical practice.

Dr. Caselli is professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.