The diagnostic performance of neurofilament light chain in CSF and blood for Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis: A systematic review and meta‐analysis

Forgrave, Lauren M.; Huei‐Ming, Matthew; Best, John R.; DeMarco, Mari L.

doi:10.1016/j.dadm.2019.08.009

Cited by 111 publications

(128 citation statements)

References 90 publications

Supporting

Mentioning

119

Contrasting

Order By: Relevance

“…Prior studies have consistently recorded high plasma NfL levels in AD compared to cognitively unimpaired controls. [43][44][45] However, plasma NfL is not specific for AD, but is elevated in multiple neurological conditions. [46][47][48] Here, we found that plasma NfL is elevated in AD and in non-AD dementias, which included subjects with FTD, DLB, and VaD.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Plasma NT1 Tau is a Specific and Early Marker of Alzheimer's Disease

Mengel

Bateman

Glynn

et al. 2020

Annals of Neurology

View full text Add to dashboard Cite

Objective There is an urgent need for sensitive, widely available, blood‐based screening tests to identify presymptomatic individuals destined to develop Alzheimer's disease (AD). We investigated whether tau detected in plasma by our in‐house NT1 assay is specifically altered in AD, and when applied to patients with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) can serve to predict progression to AD dementia. The predictive value of NT1 versus tau measured using assays from Quanterix and Roche, and the specificity of NT1 for AD versus a nonspecific marker of neurodegeneration (neurofilament light [NfL]) were also examined. Methods NT1 tau and NfL were measured in plasma from prospectively followed patients with SCD or MCI who remained cognitively stable, converted to AD dementia, or converted to non‐AD dementias, and in cognitively unimpaired participants. Tau was measured using Quanterix and Roche assays in baseline subjects with SCD and MCI. Results Plasma NT1 tau was specifically elevated in AD, but not in non‐AD dementia compared with controls, whereas NfL was increased in both AD and non‐AD dementias. Baseline specimens from individuals who had SCD or MCI revealed that NT1 tau, but not tau measured using Quanterix or Roche assays, is elevated in subjects who progress to AD dementia. As expected, baseline plasma NfL is elevated in those who progress to AD and non‐AD dementias. Interpretation Plasma NT1 tau is a specific marker of AD, which is elevated early in disease and may prove useful as a first round screen to identify individuals at risk of developing AD. ANN NEUROL 2020;88:878–892

show abstract

Section: Discussionmentioning

confidence: 99%

“…Whereas there is good agreement that NfL is elevated in both AD and other neurodegenerative diseases, 43,49 measurement of tau in plasma has yielded conflicting results. 18,24,50 This is probably due to the molecular complexity of extracellular tau 12,13,[30][31][32] and use of assays that measure different populations of tau.…”

Section: Discussionmentioning

confidence: 99%

Plasma NT1 Tau is a Specific and Early Marker of Alzheimer's Disease

Mengel

Bateman

Glynn

et al. 2020

Annals of Neurology

View full text Add to dashboard Cite

show abstract

“…In recent years, there has been strong evidence from independent groups, large cohorts of patients, and multicenter studies that neurofilament light chains are potentially valuable ALS biomarkers ( 3 , 5 – 13 , 21 , 23 ). Verde et al showed that serum NFL is increased in ALS compared to other conditions and can serve as a diagnostic and prognostic biomarker using ultrasensitive single-molecule array technology ( 6 ).…”

Section: Discussionmentioning

confidence: 99%

CSF Neurofilament Light Chain Elevation Predicts ALS Severity and Progression

et al. 2020

View full text Add to dashboard Cite

Objectives: This study compared neurofilament light chain (NFL) levels in the cerebrospinal fluid (CSF) of patients with sporadic amyotrophic lateral sclerosis (sALS) with levels in patients with other neurological diseases and healthy controls and assessed correlations between NFL levels and clinical indicators of sALS. Methods: We used enzyme-linked immunosorbent assays to determine the NFL levels in the CSF of 45 patients with sALS, 21 patients with other central nervous system diseases (OCNSDs), 18 with immune-mediated peripheral neuropathy (IMPN), 14 with non-immune-mediated peripheral neuropathy (NIMPN), and 19 healthy controls (HCs). Results: The median NFL levels in the CSF of the sALS, OCNSD, IMPN, NIMPN, and HC groups were 6510, 5372, 4320, 1477, and 756 pg/mL, respectively. The CSF NFL levels did not differ significantly among the sALS, IMPN, and OCNSD groups, but were significantly higher than those of the NIMPN and HC groups. The NFL CSF levels were significantly higher in the NIMPN group than the HCs. There was a negative correlation between the NFL level and ALS function score (ALSFRS-R), and a positive correlation with the disease progression rate in patients with sALS. Conclusion: CSF NFL may not be sufficient to distinguish ALS from other central nervous system diseases or peripheral neuropathy, but it predicts ALS severity and progression.

show abstract

“…However, our findings are in line with the results of other studies showing that CSF NfL levels are significantly higher in men compared with women in healthy individuals and several neurodegenerative diseases. 24 Most of the patients demonstrating an elevated CSF NfL measurement as the only evidence of disease activity had a progressive disease course. This observation was less apparent when looking at the clinical activity only or MRI activity only subgroups.…”

Section: Discussionmentioning

confidence: 96%

CSF neurofilament light chain testing as an aid to determine treatment strategies in MS

Reyes

Smets

Holden

et al. 2020

Neurol Neuroimmunol Neuroinflamm

View full text Add to dashboard Cite

ObjectiveTo evaluate the use of CSF neurofilament light chain (NfL) measurements in clinical practice as well as their effect on treatment strategies and outcomes in patients with MS.MethodsThis was an observational cohort study of patients with MS who had a CSF NfL measurement between December 2015 and July 2018 as part of their routine clinical care. Treatment strategies were classified as “No Treatment/No Escalation” (no treatment or no escalation of treatment) or “Treatment/Escalation” (first-line injectable/oral disease-modifying therapies (DMTs), highly active DMTs, or treatment escalation). Change in Expanded Disability Status Scale (EDSS) scores was evaluated after 1-year follow-up.ResultsOf 203 patients with MS, 117 (58%) had relapsing-remitting MS. Disease activity was most frequently indicated by elevated CSF NfL (n = 85), followed by clinical (n = 81) and MRI activity (n = 65). CSF NfL measurements were independently associated with clinical (p = 0.02) and MRI activity (p < 0.001). Of those with elevated CSF NfL as the only evidence of disease activity (n = 22), 77% had progressive MS (PMS). In patients with PMS, 17 (20%) had elevated CSF NfL as the sole indicator of disease activity. Elevated CSF NfL resulted more frequently in Treatment/Escalation than normal CSF NfL (p < 0.001). Median EDSS change at follow-up was similar between patients receiving No Treatment/No Escalation and Treatment/Escalation decisions (p = 0.81).ConclusionsCSF NfL measurements informed treatment strategies, alongside clinical and MRI measures. CSF NfL levels were the only indicator of disease activity in a subset of patients, which was more pronounced in patients with PMS. Elevated CSF NfL was associated with more Treatment/Escalation strategies, which had an impact on EDSS outcomes at 1 year.

show abstract

The diagnostic performance of neurofilament light chain in CSF and blood for Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis: A systematic review and meta‐analysis

Cited by 111 publications

References 90 publications

Plasma NT1 Tau is a Specific and Early Marker of Alzheimer's Disease

Plasma NT1 Tau is a Specific and Early Marker of Alzheimer's Disease

CSF Neurofilament Light Chain Elevation Predicts ALS Severity and Progression

CSF neurofilament light chain testing as an aid to determine treatment strategies in MS

Contact Info

Product

Resources

About