Neurofilament Light Chain Dynamics in Neurodegenerative Disorders

Neurofilament light chain (NfL) has emerged as a robust indicator of neuroaxonal injury across a broad spectrum of neurodegenerative conditions. Released into cerebrospinal fluid (CSF) and, subsequently, into blood following axonal damage, NfL concentrations reflect both acute and chronic neuronal loss. In Alzheimer’s disease, frontotemporal dementia and parkinsonian syndromes, elevations in CSF and plasma NfL correlate with brain atrophy, cognitive decline and functional impairment. The parallel measurement of NfL in CSF and blood has enabled less invasive longitudinal monitoring, facilitating both early detection—often years before symptom onset—and evaluation of therapeutic impact. Population studies have further clarified age‐dependent trajectories of NfL, underpinning its interpretation in clinical trials and routine practice. Ultimately, the dynamics of NfL offer a window into the temporal evolution of neurodegeneration, guiding diagnosis, prognosis and the development of neuroprotective strategies.

Research from Nature Portfolio

Recent comparative analyses of autosomal dominant Alzheimer’s disease have used paired CSF and plasma samples from large cohorts to chart NfL trajectories across the presymptomatic and symptomatic phases. These data reveal that NfL levels in both fluids begin to diverge from controls up to two decades before clinical onset, with rates of change in CSF continuing to rise after symptom emergence while plasma NfL plateaus. Such findings underscore the value of CSF NfL for monitoring treatment effects in symptomatic patients and of plasma NfL for population screening in at‐risk individuals. Complementary population‐based studies have characterised serum NfL in healthy ageing, demonstrating a marked acceleration of NfL increase beyond 60 years of age and close associations with cross‐sectional and longitudinal brain volume loss. These insights establish normative age‐stratified reference ranges and highlight subclinical pathology as a driver of elevated NfL in older adults.

Neurofilament Light Chain Dynamics in Neurodegenerative Disorders publication trend

The graph below shows the total number of articles in neurofilament light chain dynamics in neurodegenerative disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Neurofilament light chain (NfL): A neuron‐specific cytoskeletal protein released into extracellular fluids after axonal injury.

Cerebrospinal fluid (CSF): The clear fluid surrounding the brain and spinal cord, sampled to measure central biomarkers.

Plasma: The liquid component of blood, used to assess peripheral biomarker concentrations.

Biomarker: A measurable molecular indicator of a biological or pathological process, employed for diagnosis, prognosis or treatment monitoring.

Single molecule array (Simoa): An ultrasensitive immunoassay platform capable of detecting low‐abundance proteins in small fluid volumes.

References

1. Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer’s disease. Nature Communications (2024).
2. Introducing neurofilament light chain measure in psychiatry: current evidence, opportunities, and pitfalls. Molecular Psychiatry (2024).
3. Serum neurofilament light levels in normal aging and their association with morphologic brain changes. Nature Communications (2020).
4. Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration. Acta Neuropathologica Communications (2019).