The role of neurofilament light chain in frontotemporal dementia: a meta-analysis

Karantali, Eleni; Kazis, Dimitrios; Chatzikonstantinou, Symela; Petridis, Fivos; Mavroudis, Ioannis

doi:10.1007/s40520-020-01554-8

Cited by 43 publications

(41 citation statements)

References 45 publications

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“…Lastly, the detection and quantitation of NF-L in biofluids has become a widely researched, recognized and diagnostically valuable biomarker for the earliest detection and onset of all-cause neural decline in progressive, age-related neurodegeneration, stroke and traumatic brain injury [ 20 , 47 , 91 ]. It is becoming increasingly clear that NF-L presence in biofluids alone however, is neither specific or selective for AD or for any other progressive age-related neurological disorder [ 12 , 29 , 65 , 92 ].The highest value of measuring the abundance of NF-L as a biomarker in CSF may be to differentiate between complex neurological disorders with close and often overlapping clinical presentation, such as assisting the differentiation between FTD (the second most frequent cause of dementia, after AD in patients under the age of 65) from AD, and PD from atypical Parkinsonian syndromes [ 47 , 91 , 93 ]. Further studies on large age- and gender-matched genetically defined populations, including the application of a more personalized medicine approach for AD diagnosis and treatment [ 29 , 75 ]: (i) should provide an improved understanding of the disease mechanisms involved with NF-L liberation from neurons and NF-L accumulation in biofluids, brain dysfunction and neurodegeneration; and (ii) allow for the discovery of new biomarkers, or defined combinations of biomarkers, for disease prognosis and diagnosis that should engender equally novel therapeutic strategies [ 94 – 97 ].…”

Section: Discussionmentioning

confidence: 99%

Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery

Lukiw¹

2021

J Alzheimer’s Neurodegener Dis

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Neurofilaments (NFs) are critical scaffolding components of the axoskeleton of healthy neurons interacting directly with multiple synaptic-phosphoproteins to support and coordinate neuronal cell shape, cytoarchitecture, synaptogenesis and neurotransmission. While neuronal presynaptic proteins such as synapsin-2 (SYN II) degrade rapidly via the ubiquitin-proteasome pathway, a considerably more stable neurofilament light (NF-L) chain protein turns over much more slowly, and in several neurological diseases is accompanied by a pathological shift from an intracellular neuronal cytoplasmic location into various biofluid compartments. NF-L has been found to be significantly elevated in peripheral biofluids in multiple neurodegenerative disorders, however it is not as widely appreciated that NF-L expression within neurons undergoing inflammatory neurodegeneration exhibit a significant down-regulation in these neuron-specific intermediate-filament components. Down-regulated NF-L in neurons correlates well with the observed axonal and neuronal atrophy, neurite deterioration and synaptic disorganization in tissues affected by Alzheimer’s disease (AD) and other progressive, age-related neurological diseases. This Review paper: (i) will briefly assess the remarkably high number of neurological disorders that exhibit NF-L depolymerization, liberation from neuron-specific compartments, mobilization and enrichment into pathological biofluids; (ii) will evaluate how NF-L exhibits compartmentalization effects in age-related neurological disorders; (iii) will review how the shift of NF-L compartmentalization from within the neuronal cytoskeleton into peripheral biofluids may be a diagnostic biomarker for neuronal-decline in all cause dementia most useful in distinguishing between closely related neurological disorders; and (iv) will review emerging evidence that deficits in plasma membrane barrier integrity, pathological transport and/or vesicle-mediated trafficking dysfunction of NF-L may contribute to neuronal decline, with specific reference to AD wherever possible.

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Section: Discussionmentioning

confidence: 99%

Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery

Lukiw¹

2021

J Alzheimer’s Neurodegener Dis

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“…The protein Aβ1-42 (amyloid, Aβ), t-Ta u , and p-Ta u 181 have been employed as CSF biomarkers for AD [8]. In addition, neurofilament light chain (NFL) has recently attracted attention as a biomarker for neuroaxonal damage [9][10][11][12]. The ATN system (ATN: amyloid, tau, neurodegeneration) has been established as a multimodal classification scheme [13].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Fluid Biomarkers in Alzheimer’s Disease: Blood and Cerebrospinal Fluid

Park

Gunasekaran

Cho

et al. 2021

Preprint

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Background: Potential biomarkers for Alzheimer’s disease (AD) include amyloid β 1-42 (Aβ 1-42 ), t-Tau, p-Tau 181 , neurofilament light chain (NFL), and neuroimaging, but the feasibility of using these for the diagnosis and monitoring of AD has not been reported. Therefore, further development of these biomarkers is essential. Methods: We measured NFL and Aβ 1-42 concentrations in CSF and plasma samples from 136 participants and performed correlation analysis to evaluate the utility of these biomarkers for early diagnosis and monitoring of disease progression in AD spectrum. Results: With disease progression, concentrations of NFL increased, and those of Aβ 1-42 were decreases. The plasma and CSF values of NFL/Aβ 1-42 were strongly correlated ( r = 0.558). In addition, the plasma value of NFL/Aβ 1-42 was strong correlated with hippocampal volume/ICV ( r = 0.409). In the early stage of AD, the plasma_NFL/Aβ 1-42 was associated with higher diagnostic accuracy than were the individual biomarkers. Moreover, in preclinical AD, plasma_NFL/Aβ 1-42 changed more rapidly than did either the t-Tau or the p-Tau 181 values measured in the CSF. Conclusions: Taken together, our findings highlight the utility of plasma_NFL/Aβ 1-42 as a biomarker for early diagnosis and monitoring of disease progression in AD spectrum.

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“…In the past two decades, many efforts have been made to nd imaging or uid biomarkers for FTD [1][2][3][4][5][6] . In spite of the notable advances, we still do not have pathophysiological markers of FTD to be used in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

“…The clinical manifestation of FTD may overlap with psychiatric or other neurodegenerative disorders, such as Alzheimer's disease (AD). Diagnosis is thus a clinical challenge.In the past two decades, many efforts have been made to nd imaging or uid biomarkers for FTD [1][2][3][4][5][6] . In spite of the notable advances, we still do not have pathophysiological markers of FTD to be used in clinical practice.…”

mentioning

confidence: 99%

Plasma Glial Fibrillary Acidic Protein and Neurofilament-Light for the Diagnostic and Prognostic Evaluation of Frontotemporal Dementia

Zhu

Santos‐Santos

Illán-Gala

et al. 2021

Preprint

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Background: Astrocytes play an essential role in neuroinflammation and are involved in the pathogenesis of neurodenegerative diseases. The Study of Glial fibrillary acidic protein (GFAP), an astrocytic damage marker, may be helpful to better understand the different neurodegenerative diseases. We investigated the diagnostic performance of plasma GFAP (pGFAP), plasma neurofilament (pNfL) and their combination in frontotemporal dementia (FTD) and Alzheimer’s disease (AD). We studied their clinical utility in predicting disease progression. Methods: We measured pGFAP and pNfL concentrations in 72 FTD, 56 AD and 83 cognitively normal participants (CN) using Single Molecule Array technology. Of 211 participants, 199 had CSF and 122 had MRI. We compared cross-sectional biomarker levels between groups, studied their diagnostic performance and assessed correlation with CSF biomarkers, cognitive performance and cortical thickness. The prognostic performance was investigated analyzing cognitive decline between group comparisons by tertile. Results: Unlike pNfL, which was increased similarly in both clinical groups, pGFAP was increased in FTD but lower than in AD (all p<0.01). The combination of both plasma markers improved the diagnostic performance to discriminate FTD from AD (combination AUC 0.78; pGFAP AUC 0.7; pNfL AUC 0.61, all p<0.05). In FTD, pGFAP correlated with cognition, CSF and plasma NfL, and cortical thickness (all p<0.05). The higher tertile of pGFAP was associated with greater change in MMSE score and poor cognitive outcome during follow-up both in FTD (1.40 points annually, HR 3.82, p<0.005) and AD (1.20 points annually, HR 2.26, p<0.005).Conclusions: pGFAP and pNfL differed in FTD and AD, their combination could be useful to distinguish the two diseases. pGFAP could also be used to track disease severity and predict greater cognitive decline during follow-up in patients with FTD.

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The role of neurofilament light chain in frontotemporal dementia: a meta-analysis

Cited by 43 publications

References 45 publications

Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery

Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery

Diagnostic Fluid Biomarkers in Alzheimer’s Disease: Blood and Cerebrospinal Fluid

Plasma Glial Fibrillary Acidic Protein and Neurofilament-Light for the Diagnostic and Prognostic Evaluation of Frontotemporal Dementia

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