A multicentre validation study of the diagnostic value of plasma neurofilament light

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.

Neuroinflammation and Its Association with Cognition, Neuronal Markers and Peripheral Inflammation after Chemotherapy for Breast Cancer

“…In rodents, cytostatics increase apoptosis and reduce neurogenesis [20,21]. Promising markers to investigate neurotoxicity in humans are neurofilaments, which demonstrate high prognostic and diagnostic accuracy for neurodegenerative diseases, such as amyotrophic lateral sclerosis [22] and Alzheimer's disease [23], even in their earlier stages. Moreover, neurofilaments increase in a chemotherapy dose-dependent manner in breast cancer patients, suggesting their potential as a marker for neuronal damage after chemotherapy [24].…”

Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up

“…Due to infection control measures present at the time of the study, further neuroimaging and EEG studies were limited and generally not available for this report. This raises the question of underestimating the burden of neurology morbidity [29] , although the presence or absence of ongoing neuronal injury may be accurately assessed with NfL [30] . In addition, the wasting of peripheral nerves, a recognized feature in ICU patients, may contribute to increased NfL concentrations, although it cannot explain an increase in GFAp [31] , [32] , [33] .…”

Genotyping and Plasma/Cerebrospinal Fluid Profiling of a Cohort of Frontotemporal Dementia–Amyotrophic Lateral Sclerosis Patients

“…One limitation to our work is the rather small cohort size; however, this is counterbalanced by the depth of the genotypic and phenotypic characterization. In addition to the plasma and CSF biomarkers used in our study, there is increasing interest in the possible role of other emerging biomarkers in ALS and FTD, including neurofilaments both in CSF [ 82 , 83 ] and plasma [ 84 , 85 ]. This is of special importance for patients with the FTD/ALS phenotype, given that there is evidence that elevated Neurofilament Heavy chain (NfH) levels could antedate the onset of ALS in FTD patients [ 83 ].…”