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Association of Cerebrospinal Fluid Neurofilament Light Concentration With Alzheimer Disease Progression
Open accessAbstract
IMPORTANCE: The extent to which large-caliber axonal degeneration contributes to Alzheimer disease (AD) progression is unknown. Cerebrospinal fluid (CSF) neurofilament light (NFL) concentration is a general marker of damage to large-caliber myelinated axons. OBJECTIVE: To test whether CSF NFL concentration is associated with cognitive decline and imaging evidence of neurodegeneration and white matter change in AD. DESIGN, SETTING, AND PARTICIPANTS: A commercially available immunoassay was used to analyze CSF NFL concentration in a cohort of patients with AD (n = 95) or mild cognitive impairment (MCI) (n = 192) and in cognitively normal individuals (n = 110) from the Alzheimer's Disease Neuroimaging Initiative. The study dates were January 2005 to December 2007. The NFL analysis was performed in November 2014. MAIN OUTCOMES AND MEASURES: Correlation was investigated among baseline CSF NFL concentration and longitudinal cognitive impairment, white matter change, and regional brain atrophy within each diagnostic group. RESULTS: Cerebrospinal fluid NFL concentration (median [interquartile range]) was higher in the AD dementia group (1479 [1134-1842] pg/mL), stable MCI group (no progression to AD during follow-up; 1182 [923-1687] pg/mL), and progressive MCI group (MCI with progression to AD dementia during follow-up; 1336 [1061-1693] pg/mL) compared with control participants (1047 [809-1265] pg/mL) (P < .001 for all) and in the AD dementia group compared with the stable MCI group (P = .01). In the MCI group, a higher CSF NFL concentration was associated with faster brain atrophy over time as measured by changes in whole-brain volume (β = -4177, P = .003), ventricular volume (β = 1835, P < .001), and hippocampus volume (β = -54.22, P < .001); faster disease progression as reflected by decreased Mini-Mental State Examination scores (β = -1.077, P < .001) and increased Alzheimer Disease Assessment Scale cognitive subscale scores (β = 2.30, P < .001); and faster white matter intensity change (β = 598.7, P < .001). CONCLUSIONS AND RELEVANCE: Cerebrospinal fluid NFL concentration is increased by the early clinical stage of AD and is associated with cognitive deterioration and structural brain changes over time. This finding corroborates the contention that degeneration of large-caliber axons is an important feature of AD neurodegeneration.
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“CSF neurogranin is presumed to measure synaptic degeneration and loss [170,171], and neurofilament light chain [172] is presumed to measure axonal injury.”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [172]
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“Furthermore, several studies describe association between cognitive impairment and increased CSF (Zetterberg et al., 2016) and plasma NFL (Lin et al., 2018) in AD.”
From Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis (2020) · cites this paper as Zetterberg et al., 2016
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“neurogranin is presumed to measure synaptic degeneration and loss [170,171], and neurofilament light chain [172] is presumed to measure axonal injury.”
Self-citationNeurofilaments as biomarkers in neurological disorders
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“This exclusion may have made it difficult to detect subtle associations between plasmaNFLandwhitematter pathologic findings andmayexplain the surprising finding that plasmaNFLdid not correlate with WMHs, despite that CSF NFL has been considered a markerofwhitematterpathologic features,(26) including inAD.(7) Future st…”
InfluentialSelf-citationBlood-based biomarkers for Alzheimer's disease: towards clinical implementation
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“67,68 Concentrations of NfL increase with age, which complicates interpretation of results.”
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Self-citationNeurofilaments and Neurofilament Proteins in Health and DiseasePreprint
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Self-citationNeurofilaments as biomarkers in neurological disorders — towards clinical application
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Self-citationBacioglu, M., Maia, L. F., Preische, O., Schelle, J., Apel, A., Kaeser, S. A., Schweighauser, M., Eninger, T., Lambert, M., Pilotto, A., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.05.018 · Cited by 435
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Self-citationThe diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease
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“In this context, CSF levels of amyloid-b42, tau and, more recently, neurofilament light chain (NfL) proteins have been associated with cognition and Alzheimer’s disease (Mattsson et al., 2016a, 2017; Zetterberg et al., 2016; Olsson et al., 2019).”
Neurofilaments: neurobiological foundations for biomarker applications
Gafson, A., Barthélemy, N. R., Bomont, P., Carare, R. O., Durham, H. D., Julien, J., Kühle, J., Leppert, D., Nixon, R. A., Weller, R. O., et al. (2020) · Brain · doi:10.1093/brain/awaa098 · Cited by 339
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BackgroundSelf-citationWeiner, M. W., Veitch, D. P., Aisen, P. S. S., Beckett, L. A., Cairns, N. J., Green, R. C., Harvey, D. J., Jack, C. R., Jagust, W. J., Morris, J. C., et al. (2017) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.11.007 · Cited by 325
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“It has now, however, become evident that CSF NF-L increase is an inherent feature of AD, and that increased CSF NF-L concentrations, along with biomarker evidence of classical AD pathology, predict a more rapid disease progression (Zetterberg et al. 2016).”
BackgroundSelf-citationPlasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease
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Self-citationCerebrospinal fluid tau, neurogranin, and neurofilament light in Alzheimer's disease
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“But CSF NFL is also relevant in AD (Zetterberg et al, 2016) since AD not only involves loss of cortical structures but also white matter injury (Migliaccio et al, 2012) and disconnection of cortical and subcortical regions (Delbeuck et al, 2003).”
Self-citationNeurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies
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Plasma and CSF neurofilament light
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Self-citationNeurofilament light chain: a biomarker for genetic frontotemporal dementia
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“The identified correlations of NfL levels with disease severity and survival in genetic FTD patients are also in line with earlier reports in sporadic FTD, AD, and ALS.(10,11,13,18) Specifically, the association of high NfL levels with a poor survival could serve as a meaningful prognostic clinical tool.”
BackgroundResultInfluentialYiannopoulou, K. G., Anastasiou, A. I., Zachariou, V., & Pelidou, S.-H. (2019) · Biomedicines · doi:10.3390/biomedicines7040097 · Cited by 330
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“Another CSF biomarker for axonal degeneration is neurofilament light (NF-L; NEFL), which is a structural protein present in long axons (Zetterberg, 2016).”
InfluentialSelf-citationBiomarkers for the Early Detection and Progression of Alzheimer's Disease
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“This is in agreement with NfL being a biomarker of nonspecific axonal degeneration (Zetterberg et al , 2016; Bridel et al , 2019), but these results should be confirmed in an independent cohort.”
ResultSelf-citationNeth, B. J., Mintz, A., Whitlow, C. T., Jung, Y., Sai, K. K. S., Register, T. C., Kellar, D., Lockhart, S. N., Hoscheidt, S. M., Maldjian, J. A., et al. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.09.015 · Cited by 219
“Supporting this possibility, we also found trend-level reduction of CSF neurogranin and NFL after MMKD, suggesting diet may have impact on measures of dendritic/synaptic injury and neurodegeneration (Blennow and Zetterberg, 2018; Zetterberg et al., 2016).”
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“In support of this, elevated amounts of NfL in CSF have been observed in patients across several adult neurodegenerative diseases, including Alzheimer’s disease and frontotemporal dementia (52, 53).”
BackgroundUntangling the association of amyloid-β and tau with synaptic and axonal loss in Alzheimer’s disease
Pereira, J. B., Janelidze, S., Ossenkoppele, R., Kvartsberg, H., Brinkmalm, A., Mattsson, N., Stomrud, E., Smith, R. A., Zetterberg, H., Blennow, K., et al. (2020) · Brain · doi:10.1093/brain/awaa395 · Cited by 208
Self-citationValidation of Serum Neurofilament Light Chain as a Biomarker of Parkinson's Disease Progression
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Self-citationDiagnostic biomarkers of Alzheimer’s disease: A state-of-the-art review
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“DM is supported by an impact on “downstream” measures of cell death such as MRI atrophy, CSF tau, or possibly other biomarkers of neuronal degeneration such as neurofilament light chain protein [54].”
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“In our study, CSF NfL concentration was significantly higher in the MCI-AD/AD-dem group as compared with both PD and control subjects, in line with similar results obtained in previous studies [5, 44].”
InfluentialSelf-citationRevolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology
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ResultDetection and treatment of Alzheimer’s disease in its preclinical stage
Rafii, M. S., & Aisen, P. S. S. (2023) · Nature Aging · doi:10.1038/s43587-023-00410-4 · Cited by 179
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Biomarkers used in Alzheimer’s disease diagnosis, treatment, and prevention
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“We included Nfl in analyses since it has been shown to predict cognitive decline in ADNI and other studies [31,32].”
ResultBiomarkers for Alzheimer’s Disease Early Diagnosis
Ausó, E., Gómez‐Vicente, V., & Esquiva, G. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10030114 · Cited by 159
“Regarding neuronal damage, some proteins such as neurofilament light chain (NF-L), a protein involved in protecting neurites, and neuron-specific enolase (NSE), which plays a role in neuronal metabolism, have revealed increased CSF concentrations in MCI patients in comparison with cognitively elderly, and with patient…”
BackgroundResultSleep disturbances and dementia risk: a multicenter study
Sindi, S., Kåreholt, I., Johansson, L., Skoog, J., Sjöberg, L., Wang, H., Johansson, B., Fratiglioni, L., Soininen, H., Solomon, A., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.05.012 · Cited by 144
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Knopman, D. S., Haeberlein, S. B., Carrillo, M. C., Hendrix, J. A., Kerchner, G., Margolin, R. A., Maruff, P. T., Miller, D. S., Tong, G., Tome, M. B., et al. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.03.002 · Cited by 144
“Among the most promising biomarkers are CSF and plasma neurofilament light chain [40,41], and CSF neurogranin [42], visinin-like protein-1 [43], YKL-40 (an inflammatory marker) [44], and fatty acid–binding protein 3 [45].”
BackgroundSelf-citationAlirezaei, Z., Pourhanifeh, M. H., Borran, S., Nejati, M., Mirzaei, H., & Hamblin, M. R. (2020) · Molecular Neurobiology · doi:10.1007/s12035-019-01698-3 · Cited by 142
Hulle, C. V., Jonaitis, E. M., Betthauser, T. J., Batrla, R., Wild, N., Kollmorgen, G., Andréasson, U., Okonkwo, O. C., Bendlin, B. B., Asthana, S., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12204 · Cited by 132
“The following immunoassays were performed on a cobas e 601 analyzer: Elecsys β-amyloid(1-42) CSF, Elecsys Phospho-Tau (181P) CSF and Elecsys Total-Tau CSF, S100 calcium binding protein B (S100B), and interleukin-6 (IL6).”
MethodSelf-citationCerebrospinal Fluid Biomarkers for Early and Differential Alzheimer’s Disease Diagnosis
Bjerke, M., & Engelborghs, S. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170680 · Cited by 137
The implications of different approaches to define AT(N) in Alzheimer disease
Mattsson-Carlgren, N., Leuzy, A., Janelidze, S., Palmqvist, S., Stomrud, E., Strandberg, O., Smith, R., & Hansson, O. (2020) · Neurology · doi:10.1212/wnl.0000000000009485 · Cited by 114
“CSF Aβ (Aβ42), tau phosphorylated at Thr181 (p-tau), and neurofilament light (NfL) were quantified using ELISAs (Aβ42 and p-tau: BioFINDER-1, EUROIMMUN AG, Lub̈eck, Germany; BioFINDER-2, INNOTEST, Fujirebio, Ghent, Belgium; NfL: Uman Diagnostics, Umeå, Sweden).(7) CSF analyses were performed in accordance with the Alz…”
MethodSelf-citationPaterson, R. W., Slattery, C. F., Poole, T., Nicholas, J. M., Magdalinou, N. K., Toombs, J., Chapman, M. D., Lunn, M. P., Heslegrave, A., Foiani, M. S., et al. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0361-3 · Cited by 130
“NFL is thought to be a marker of large axonal neurodegeneration [35] and is elevated in a number of non-AD diseases [36–38], particularly FTD and motor neurone disease [39].”
BackgroundSelf-citationNeuroimaging and fluid biomarkers in Parkinson’s disease in an era of targeted interventions
Zarkali, A., Thomas, G. E. C., Zetterberg, H., & Weil, R. S. (2024) · Nature Communications · doi:10.1038/s41467-024-49949-9 · Cited by 131
“However, NFL is a non-speci fi c marker and rises in relation to white matter lesions across in fl ammatory and other degenerative conditions 187,188 , and with age, Perspective https://doi.org/10.1038/s41467-024-49949-9 Nature Communications| (2024) 15:5661 which may limit its use in clinical…”
BackgroundInfluentialSelf-citationHoy, A. R., Ly, M., Carlsson, C. M., Okonkwo, O. C., Zetterberg, H., Blennow, K., Sager, M. A., Asthana, S., Johnson, S. C., Alexander, A. L., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0173982 · Cited by 131
Self-citationLleó, A., Alcolea, D. A., Martínez‐Lage, P., Scheltens, P., Parnetti, L., Poirier, J., Simonsen, A. H., Verbeek, M. M., Rosa‐Neto, P., Slot, R. E. R., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.01.015 · Cited by 130
“Tau is a protein predominantly expressed in cortical brain regions, and tau levels in CSF could be a reflection of hippocampal and cortical atrophy, whereas NfL levels could be a reflection of subcortical damage [37,41].”
BackgroundSelf-citationClinical value of neurofilament and phospho-tau/tau ratio in the frontotemporal dementia spectrum
Meeter, L. H. H., Vijverberg, E. G., Del Campo, M., Rozemuller, A. J. M., Donker Kaat, L., de Jong, F. J., van der Flier, W. M., Teunissen, C. E., van Swieten, J. C., & Pijnenburg, Y. A. L. (2018) · Neurology · doi:10.1212/wnl.0000000000005261 · Cited by 122
Bos, I., Vos, S. J. B., Verhey, F. R. J., Scheltens, P., Teunissen, C. E., Engelborghs, S., Sleegers, K., Frisoni, G. B., Blin, O., Richardson, J. C., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.01.004 · Cited by 122
“High concentrations of neurofilament-light (NFL) have been 17 associated with axonal degeneration to, predominantly, subcortical brain areas [7, 8] and YKL18 40 (also known as chitinase 3-like protein 1) concentrations were found to reflect astrocytic 19 activation, an inflammatory response to neurodegenerative proces…”
BackgroundMethodSelf-citationBenedet, A. L., Leuzy, A., Pascoal, T. A., Ashton, N. J., Mathotaarachchi, S. S., Savard, M., Therriault, J., Kang, M. S., Chamoun, M., Schöll, M., et al. (2020) · Brain · doi:10.1093/brain/awaa342 · Cited by 126
“One such potential measure is the axonal injury marker neurofilament light (NfL) (Zetterberg, 2016).”
Self-citationXia, D., Lianoglou, S., Sandmann, T., Calvert, M., Suh, J. H., Thomsen, E., Dugas, J., Pizzo, M. E., DeVos, S. L., Earr, T. K., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00547-7 · Cited by 124
Leveraging preclinical models for the development of Alzheimer disease therapeutics
Scearce-Levie, K. A., Sanchez, P. E., & Lewcock, J. W. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0065-9 · Cited by 121
Hampel, H., Toschi, N., Baldacci, F., Zetterberg, H., Blennow, K., Kilimann, I., Teipel, S. J., Cavedo, E., Melo dos Santos, A., Epelbaum, S., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2017.11.015 · Cited by 129
“These outcomes are consistent with a recent analysis reporting the association between CSF NFL concentration and cognitive impairment [35].”
Self-citationPereira, J. B., Westman, E., & Hansson, O. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.06.002 · Cited by 120
Oligomeric Aβ in the monkey brain impacts synaptic integrity and induces accelerated cortical aging
Beckman, D., Ott, S., Donis-Cox, K., Janssen, W. G., Bliss-Moreau, E., Rudebeck, P. H., Baxter, M. G., & Morrison, J. H. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1902301116 · Cited by 111
“Neurofilament light (NFL), a structural component of the cytoskeleton of some neurons, is increased in the CSF of patients with AD as a reflection of degeneration of large-caliber axons (56).”
BackgroundSerum neurofilament light chain in behavioral variant frontotemporal dementia
Steinacker, P., Anderl-Straub, S., Diehl-Schmid, J., Semler, E., Uttner, I., von Arnim, C. A. F., Barthel, H., Danek, A., Fassbender, K., Fliessbach, K., et al. (2018) · Neurology · doi:10.1212/wnl.0000000000006318 · Cited by 116
The CSF neurofilament light signature in rapidly progressive neurodegenerative dementias
Abu‐Rumeileh, S., Capellari, S., Maserati, M. S., Polischi, B., Martinelli, P., Caroppo, P., Ladogana, A., & Parchi, P. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-017-0331-1 · Cited by 119
“Taken together, these data indicate that the pathophysiological mechanisms leading to a more rapid course in AD involve mainly the extracellular space of the cortical gray matter and are relatively independent from those affecting NfL and αsynuclein CSF levels [28, 29, 46].”
Dhiman, K., Blennow, K., Zetterberg, H., Martins, R. N., & Gupta, V. B. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03040-5 · Cited by 117
Self-citationNeurochemical Aftermath of Repetitive Mild Traumatic Brain Injury
Shahim, P., Tegner, Y., Gustafsson, B., Gren, M., Ärlig, J., Olsson, M. A., Lehto, N., Engström, Å. H., Höglund, K., Portelius, E., et al. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.2038 · Cited by 118
Self-citationCSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP
Rojas, J. C., Bang, J., Lobach, I. V., Tsai, R. M., Rabinovici, G. D., Miller, B. L., Boxer, A. L., AL-108-231 Investigators, Williams, D. R., Lafontaine, A. L., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000004859 · Cited by 113
Alawode, D. O. T., Heslegrave, A., Ashton, N. J., Karikari, T. K., Simrén, J., Montoliu‐Gaya, L., Pannee, J., O’Connor, A., Weston, P. S. J., Lantero‐Rodriguez, J., et al. (2021) · Journal of Internal Medicine · doi:10.1111/joim.13332 · Cited by 107
Self-citationPlasma neurofilament light chain levels in Alzheimer’s disease
Zhou, W., Zhang, J., Ye, F., Xu, G., Su, H., Su, Y., & Zhang, X. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.04.027 · Cited by 95
López‐Sanz, D., Bruña, R., Garcés, P., Cámara, C., Serrano, N., Rodríguez‐Rojo, I. C., Delgado‐Losada, M. L., Montenegro, M. V. R., López-Higes, R., Yus, M., et al. (2016) · Scientific Reports · doi:10.1038/srep37685 · Cited by 106
Jin, M., Cao, L., & Dai, Y. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00254 · Cited by 105
“…26 AD 67 ± 8 57.69 1,595 ± 1,005 32 ± 16 545 ± 226 659 ± 268 78 ± 34 Vogt et al., 2018 40 AD 71.9 ± 8.6 40 1,628 ± 935 722 ± 300 74.7 ± 27 Landqvist Waldö et al., 2013 20 AD 72 ± 10 65 415 ± 309 285 ± 92 630 ± 621.9 87 ± 58 Weston et al., 2017 48 AD-fam 40.5 ± 8.2 45.83 25 ± 12 Weston et al.,…”
InfluentialKern, S., Syrjanen, J. A., Blennow, K., Zetterberg, H., Skoog, I. G., Wærn, M., Hagen, C. E., van Harten, A. C., Knopman, D. S., Jack, C. R., et al. (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2018.3459 · Cited by 100
Self-citationNeurofilament-Light, a Promising Biomarker: Analytical, Metrological and Clinical Challenges
Coppens, S., Lehmann, S., Hopley, C. J., & Hirtz, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411624 · Cited by 107
Dhiman, K., Gupta, V. B., Villemagne, V. L., Eratne, D., Graham, P. L., Fowler, C., Bourgeat, P., Li, Q., Collins, S., Bush, A. I., et al. (2020) · Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring · doi:10.1002/dad2.12005 · Cited by 93
Self-citationWang, S.-Y., Chen, W., Xu, W., Li, J., Hou, X., Ou, Y., Yu, J., & Tan, L. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190615 · Cited by 95
“AD was reported in 12 studies [18–29] with 620 AD patients and 553 controls.”
New fluid biomarkers tracking non-amyloid-β and non-tau pathology in Alzheimer’s disease
Park, S. A., Han, S. M., & Kim, C. E. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0418-9 · Cited by 96
Biomarkers in Neurodegenerative Diseases
Jeromin, A., & Bowser, R. (2017) · Advances in Neurobiology · doi:10.1007/978-3-319-57193-5_20 · Cited by 92
Current advances in plasma and cerebrospinal fluid biomarkers in Alzheimer's disease
Leuzy, A., Cullen, N. C., Mattsson, N., & Hansson, O. (2021) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000904 · Cited by 91
Self-citationThe dynamics of biomarkers across the clinical spectrum of Alzheimer's disease
Hadjichrysanthou, C., Evans, S., Bajaj, S., Siakallis, L. C., McRae-McKee, K., de Wolf, F., Anderson, R. M., & Initiative, T. A. D. N. (2020) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00636-z · Cited by 86
“…A β 1 – 42 , which indicates brain amyloid pathology [39]; the neuro-filament light (NfL), a biomarker of neuroaxonal injury or neurodegeneration [40]; the total tau (t-tau) and phosphorylated tau (p-tau) proteins [39], which can be considered as potential biomarkers of Alzheimer-type axonal…”
Litvinchuk, A., Huynh, T. V., Shi, Y., Jackson, R. J., Finn, M. B., Manis, M., Francis, C. M., Tran, A. C., Sullivan, P. M., Ulrich, J. D., et al. (2021) · Annals of Neurology · doi:10.1002/ana.26043 · Cited by 91
Hajjar, I. M., Yang, Z., Okafor, M. O., Liu, C., Waligórska, T., Goldstein, F. C., & Shaw, L. M. J. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.35068 · Cited by 89
Self-citationMilanini, B., & Valcour, V. (2017) · Current HIV/AIDS Reports · doi:10.1007/s11904-017-0361-0 · Cited by 95
Zerr, I., Schmitz, M., Karch, A., Villar‐Piqué, A., Kanata, Ε., Golańska, E., Lucena, D. D., Karsanidou, A., Hermann, P., Knipper, T., et al. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2017.12.008 · Cited by 88
“In recent studies, CSF NFL levels have been associated with cognitive deterioration and disease severity in AD and FTD [4,6,7].”
BackgroundSelf-citationSpecialized roles of neurofilament proteins in synapses: Relevance to neuropsychiatric disorders
Yuan, A., & Nixon, R. A. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.09.002 · Cited by 88
“CSF NFL concentration is increased by the early clinical stage of AD, correlates with cognitive deterioration and structural changes over time [194] and may be a useful marker of disease progression in AD [7].”
Current Biomarkers for Alzheimer’s Disease: From CSF to Blood
Zou, K., Abdullah, M., & Michikawa, M. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10030085 · Cited by 87
“showed that higher CSF NF-L concentrations are associated with cognitive deterioration and brain atrophy over time in AD and MCI groups, indicating that CSF NF-L can be used as a marker for AD progression [49].”
BackgroundNeurofilaments in disease: what do we know?
Gordon, B. A. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2020.02.001 · Cited by 82
Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview
Bălașa, A. F., Chircov, C., & Grumezescu, A. M. (2020) · Biomedicines · doi:10.3390/biomedicines8100421 · Cited by 86
Neurofilament changes in serum and cerebrospinal fluid after acute ischemic stroke
Pujol-Calderón, F., Portelius, E., Zetterberg, H., Blennow, K., Rosengren, L., & Höglund, K. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.12.042 · Cited by 84
Self-citationApplying the ATN scheme in a memory clinic population
Altomare, D., de Wilde, A., Ossenkoppele, R., Pelkmans, W., Bouwman, F. H., Groot, C., van Maurik, I. S., Zwan, M. D., Yaqub, M. M., Barkhof, F., et al. (2019) · Neurology · doi:10.1212/wnl.0000000000008361 · Cited by 81
Andersson, E., Janelidze, S., Lampinen, B., Nilsson, M., Leuzy, A., Stomrud, E., Blennow, K., Zetterberg, H., & Hansson, O. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.07.018 · Cited by 80
“In addition, NfL in both CSF and plasma were higher in patients with MCI and AD dementia compared to CU subjects, as reported by others (Mattsson et al., 2017, 2019; Olsson et al., 2019; Zetterberg et al., 2016), suggesting that NfL tracks neurodegeneration.”
BackgroundResultSelf-citationLoeffler, D. A. (2023) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-230025 · Cited by 90
“CSF NfL increases during normal aging and AD [266] and is positively associated with AD progression [269–271], increased ventricular volume [270], and hippocampal atrophy [272].”
BackgroundAn overview of the genes and biomarkers in Alzheimer’s disease
Krishnamurthy, H. K., Jayaraman, V., Krishna, K., Wang, T., Bei, K., Changalath, C., & Rajasekaran, J. J. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102599 · Cited by 89
Metadata
- Authors
- Zetterberg, H., Skillbäck, T., Mattsson, N., Trojanowski, J. Q., Portelius, E., Shaw, L. M., Weiner, M. W., Blennow, K., & Initiative, F. T. A. D. N.
- Affiliations
- UCL Queen Square Institute of Neurology (GB)
- University of Gothenburg (SE)
- University of California, San Francisco (US)
- University of Pennsylvania (US)
- Corresponding author
- Zetterberg, Henrik
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2016-01-01
- Volume
- 73
- Issue
- 1
- Pages
- 60
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC5624219
- OpenAlex
- W1934117767
- Cited by
- 487
- References
- 31
- Citations by year
- 2026: 20 · 2025: 38 · 2024: 62 · 2023: 42 · 2022: 65 · 2021: 60 · 2020: 62 · 2019: 41 · 2018: 48 · 2017: 35 · 2016: 14
- FWCI
- 26.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- U.S. Department of Defense (U01 AG024904, AG024904)
- Alzheimer's Disease Neuroimaging Initiative (W81XWH-12-2–0012, U01AG024904, AG024904, W81XWH-12-2-)
- National Institutes of Health (5u01ag024904-10, W81XWH-12-2-0012, U01-AG024904, AG024904)
- Canadian Institutes of Health Research
- National Institute on Aging (U01-AG-024904, P30AG010129, K01AG030514, P30AG013846, U24AG021886)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- neurofilament light chain, cerebrospinal fluid biomarkers, mild cognitive impairment, cognitive decline, axonal degeneration, brain atrophy, hippocampal volume, ventriculomegaly, neurodegeneration, Alzheimer's Disease Neuroimaging Initiative, biomarker validation, white matter hyperintensities, amyloid PET, tau PET
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Follow-Up Studies, Humans, Male, Cohort Studies, Biomarkers, Neurofilament Proteins, Disease Progression, Cognitive Dysfunction
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