Abstract
Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King’s College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.
Highlights
Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can be assessed in blood
In the KCL cohort, the concentrations of plasma NfL were significantly increased in all cognitively impaired, parkinsonian, DSAD, and ALS compared to the cognitively unimpaired (CU) Aβ− group (P < 0.0001, Fig. 1A), with the exception of Parkinson’s disease (PD), DS, depression, and EOAD groups
We found that in individuals >65 years, plasma NfL had relatively good accuracy in identifying neurodegenerative disorders from controls (AUC = 0.829, 95% confidence intervals (CI), 0.82–0.86; Fig. 4A) but was less accurate if PD patients were included in the neurodegenerative disorder group (AUC = 0.74, 95% CI, 0.69–0.78; Fig. 4A)
Summary
Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can be assessed in blood. Axonal degeneration or injury is a predominant feature of many neurodegenerative disorders that results in irreversible impairment In response to such damage, neurofilament light chain (NfL), a structural component of the neural cytoskeleton, is released into the extracellular space initiating a concentration increase in the CSF3. The context of the use of a blood biomarker, such as NfL, is in primary care or memory clinics care where it could be used as a rapid screening tool to identify or reject neurodegeneration as an underlying cause of cognitive symptoms30 To achieve this at the individual level, reference values to indicate neurodegeneration need to be established which results in a low rate of false positives
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