Plasma neurofilament light chain levels in Alzheimer’s disease

Zhou, Wenjun; Zhang, Jie; Ye, Fanlong; Xu, Guangzheng; Su, Hang; Su, Yindan; Zhang, Xiangyang

doi:10.1016/j.neulet.2017.04.027

Cited by 86 publications

(94 citation statements)

References 16 publications

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“…In AD, plasma or serum levels of NF-L have been shown to be elevated compared with controls in presymptomatic individuals known to be carriers of AD-causing gene mutations [385] and subjects with MCI or AD [240, 408]. Furthermore, blood-based NF-L appears to correlate with poor cognition and brain atrophy [240, 385].…”

Section: Other Neuronal Proteinsmentioning

confidence: 99%

Current state of Alzheimer’s fluid biomarkers

et al. 2018

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific context of use (COU). These COUs include, but are not limited to, subject/patient selection, assessment of disease state and/or prognosis, assessment of mechanism of action, dose optimization, drug response monitoring, efficacy maximization, and toxicity/adverse reactions identification and minimization. The core AD CSF biomarkers Aβ42, t-tau, and p-tau are recognized by research guidelines for their diagnostic utility and are being considered for qualification for subject selection in clinical trials. However, there is a need to better understand their potential for other COUs, as well as identify additional fluid biomarkers reflecting other aspects of AD pathophysiology. Several novel fluid biomarkers have been proposed, but their role in AD pathology and their use as AD biomarkers have yet to be validated. In this review, we summarize some of the pathological mechanisms implicated in the sporadic AD and highlight the data for several established and novel fluid biomarkers (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, α-synuclein, TDP-43, ferritin, VILIP-1, and NF-L) associated with each mechanism. We discuss the potential COUs for each biomarker.

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Section: Other Neuronal Proteinsmentioning

confidence: 99%

Current state of Alzheimer’s fluid biomarkers

et al. 2018

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“…Twelve studies compared blood (i.e., plasma and serum) NfL concentration in AD cases and cognitively unimpaired controls [4,9,25,30,42,[47][48][49][50][51][52][53]; however, three of these studies used largely overlapping data from the ADNI database [49,50,53]. To avoid bias, the largest of the three overlapping studies was selected for inclusion in the meta-analysis [53]; thus, 10 studies comparing 471 AD cases to 518 cognitively unimpaired controls were included in the meta-analysis. The average AD to control blood NfL concentration ratio was 2.61 (95% CI 1.54-4.44, P 5 0.003; Fig.…”

Section: Nfl In Admentioning

confidence: 99%

“…2D). Of these studies, 5 studies (365 AD cases and 357 cognitively unimpaired controls) compared NfL concentration in plasma, with an average ratio of 2.11 (95% CI 0.78-5.73) [25,30,47,48,53]. The remaining 5 studies (106 AD cases and 161 cognitively unimpaired controls) compared serum NfL concentration [4,9,42,51,52], with an average ratio of 3.22 (95% CI 1.37-7.57).…”

Section: Nfl In Admentioning

confidence: 99%

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

Huei‐Ming

Best

et al. 2019

Alz & Dem Diag Ass & Dis Mo

126

134

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Introduction A systematic review and meta‐analysis was performed regarding the diagnostic performance of neurofilament light chain (NfL) in CSF and blood. Methods A database search was conducted for NfL biomarker studies in the context of Alzheimer's disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS) compared with controls (i.e., cognitively unimpaired, mild cognitive impairment, or disease mimics). Results In groups with a sufficient number of studies, the performance of NfL in blood and CSF was similar. Compared with disease mimics, we observed that CSF NfL had strong discriminatory power for ALS, modest discriminatory power for FTD, and no discriminatory power for AD. NfL provided the greatest separation between ALS and cognitively unimpaired controls in both the blood and CSF, followed by FTD (CSF and blood), then AD (blood and CSF). Discussion Comparable performance of CSF and blood NfL in many groups demonstrates the promise of NfL as a noninvasive biomarker of neurodegeneration; however, its utility in clinically meaningful scenarios requires greater scrutiny. Toward clinical implementation, a more comprehensive understanding of NfL concentrations in disease subtypes with overlapping phenotypes and at defined stages of disease, and the development of a harmonization program, are warranted.

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“…The most recent studies using single molecule array (Simoa) technique for NFL determination have shown significantly higher serum NFL levels in the AD group even in prodromal stadium compared to normal controls. However the overlap between the AD and other diagnostic groups was obvious 14,15 . Despite this limitation plasma NFL levels may be a useful noninvasive biomarker of neurodegenerative processes 15 .…”

Section: Discussionmentioning

confidence: 95%

“…Correlation of CSF NFL with accelerated cognitive decline, changes in white matter and increased brain atrophy is found in patients with mild cognitive impairment 12 . Recently, elevated NFL levels were also described in the serum/plasma of AD patients [13][14][15] . NFH elevation in CSF seems to be less prominent in AD.…”

Section: Introductionmentioning

confidence: 97%

Neurofilaments and tau proteins in cerebrospinal fluid and serum in dementias and neuroinflammation

Fialová¹,

Bartoš²,

Švarcová³

2017

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Aims. The aim of this study was to evaluate the diagnostic potential of cerebrospinal fluid (CSF) and serum levels of neurocytoskeletal proteins and their ratios for the diagnosis of dementias and to assess the differences in neurocytoskeletal proteins between neurodegeneration and neuroinflammation. Methods. CSF and serum levels of neurofilament light subunits (NFL) and neurofilament heavy subunits (NFH) as well as CSF levels of total tau (t-tau) and phosphorylated tau (p-tau) proteins were determined using ELISA in 20 Alzheimer's disease patients (AD group), 13 patients with other dementias (OD group), 17 patients with inflammatory aseptic neuro-infections (IP), and 20 aged-matched cognitively normal elderly persons (NC group). Results. The ratio CSF p-tau/t-tau was significantly higher in the NC group than that in the AD or OD groups (P<0.0005 for each group). The CSF NFH/p-tau and CSF NFL/p-tau ratios were significantly lower in AD patients than OD patients (P≤0.003). Serum and CSF NFL and CSF NFH levels were significantly higher in OD patients than AD patients (P≤0.03).The lowest values of the CSF NFL/NFH ratio were found in the IP group and they significantly differed from those in normal controls (P<0.0001) and any dementia group (IP vs. AD P<0.0001; IP vs. OD P=0.03). Conclusion. CSF tau proteins and their index differentiated between AD or OD patients and cognitively normal subjects, while CSF levels of neurofilaments expressed as their index seem to contribute to the discrimination between patients with neuroinflammation and normal controls or AD patients.

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Plasma neurofilament light chain levels in Alzheimer’s disease

Cited by 86 publications

References 16 publications

Current state of Alzheimer’s fluid biomarkers

Current state of Alzheimer’s fluid biomarkers

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

Neurofilaments and tau proteins in cerebrospinal fluid and serum in dementias and neuroinflammation

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