Diagnostic and prognostic power of CSF Tau in amyotrophic lateral sclerosis

Scarafino, Antonio; D’Errico, Eustachio; Introna, Alessandro; Fraddosio, Angela; Distaso, Eugenio; Tempesta, Irene; Morea, Anna; Mastronardi, Antonella; Leante, Rosaria; Ruggieri, Maddalena; Mastrapasqua, Mariangela; Simone, Isabella Laura

doi:10.1007/s00415-018-9008-3

Cited by 32 publications

(57 citation statements)

References 40 publications

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“…Conversely, another study showed that elevated levels of Aβ1-42 were associated with shorter survival [26]. A previous study found that total Tau was associated with shorter survival and higher progression rate, but not with ASLFRS-R [15]. Our study also reinforces previous findings showing that levels of total Tau, phospho-Tau, or the phospho-Tau/total Tau ratio were not correlated with survival [27].…”

Section: Mild Prognosis Role Of Phospho-tau and Total Tau In Alssupporting

confidence: 85%

“…Phosphorylated-Tau protein is associated with the pathophysiology of Alzheimer's disease (AD), and is increased in AD as well [4][5][6][7]. In ALS, studies report opposite results [8][9][10][11][12], and some groups suggest that levels of CSF Tau at baseline could be correlated with disease progression [13][14][15]. Moreover, alterations in the amyloid processing protein (APP) and amyloid β1-42 peptide have been shown in the CSF and spinal cord of ALS patients [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Aβ1-42 and Tau as Potential Biomarkers for Diagnosis and Prognosis of Amyotrophic Lateral Sclerosis

Lanznaster

Hergesheimer

Bakkouche

et al. 2020

IJMS

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Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, but its definitive diagnosis delays around 12 months. Although the research is highly active in the biomarker field, the absence of specific biomarkers for diagnosis contributes to this long delay. Another strategy of biomarker identification based on less specific but sensitive molecules may be of interest in clinical practice. For example, markers related to other neurodegenerative diseases such as Alzheimer’s disease (AD) could be fully explored. Here, we compared baseline levels of amyloidβ1-42 (Aβ1-42), total Tau, and phosphorylated-Tau (phospho-Tau) protein in the cerebrospinal fluid (CSF) of ALS patients to controls and correlated it with clinical parameters of ALS progression collected over 12 months. We observed increased levels of Aβ1-42 (controls: 992.9 ± 358.3 ng/L; ALS: 1277.0 ± 296.6 ng/L; p < 0.0001) and increased Aβ1-42/phospho-Tau ratio and Innotest Amyloid Tau Index (IATI) (both p < 0.0001). IATI and the phospho-Tau/total Tau ratio correlated positively with ALSFRS-R and weight at baseline. Multivariate analysis revealed that baseline ALSFRS-R was associated with Aβ1-42 and phospho-Tau/total Tau ratio (p = 0.0109 and p = 0.0013, respectively). Total Tau and phospho-Tau levels correlated negatively with ALSFRS-R variation at months 6 and 9, respectively (p = 0.02 and p = 0.04, respectively). Phospho-Tau/total Tau ratio correlated positively with ALSFRS-R variation at month 9 (p = 0.04). CSF levels of Aβ1-42 could be used as a complementary tool to ALS diagnosis, and total Tau and phospho-Tau levels may help establishing the prognosis of ALS. Further studies merit exploring the pathophysiological mechanisms associated with these markers. Despite their lack of specificity, phospho-Tau/total Tau and Aβ1-42 should be combined to other biological and clinical markers in order to improve ALS management.

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Section: Mild Prognosis Role Of Phospho-tau and Total Tau In Alssupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Aβ1-42 and Tau as Potential Biomarkers for Diagnosis and Prognosis of Amyotrophic Lateral Sclerosis

Lanznaster

Hergesheimer

Bakkouche

et al. 2020

IJMS

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“…Sixteen studies investigated CSF NfL concentration in 930 ALS cases compared with 593 cognitively unimpaired controls [4,27,34,41,[57][58][59][64][65][66][67][68][69][70][71], with an average CSF NfL concentration ratio of 9.64 (95% CI 6.65-13.99, P , 0.0001; Fig. 4A).…”

Section: Nfl In Alsmentioning

confidence: 99%

“…In addition, 11 studies investigated CSF NfL concentration of 1239 ALS cases compared with 806 disease mimic controls, with an average concentration ratio of 3.35 (95% CI 2.19-5.12, P , 0.0001; Fig. 4B) [4,8,27,57,65,68,69,[72][73][74][75].…”

Section: Nfl In Alsmentioning

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

118

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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“…Disruption of neurofilament organisation is one of the key characteristics of many neurological conditions, such as amyotrophic lateral sclerosis (ALS), AD, FTD or vascular dementia among others 6,9,10 . In addition, recent studies have shown that levels of NfL in CSF are associated with clinical progression and severity in ALS [11][12][13] and in other neurodegenerative diseases due to its capacity to reflect the extent of neuro-axonal damage 14,15 . Recently, a large control-case study that included various neurodegenerative disorders confimed the importance of CSF NfL in the evaluation and follow-up of patients with cognitive impairment 16 : in particular, CSF NfL levels were increased in patients with a diagnosis of MCI, AD, FTD or ALS compared to controls, thus reflecting the intensity of neurodegenerative processes.…”

mentioning

confidence: 99%

Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders

Delaby

Alcolea

Carmona-Iragui

et al. 2020

Sci Rep

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Cerebrospinal fluid (CSF) biomarkers are useful in the diagnosis and the prediction of progression of several neurodegenerative diseases. Among them, CSF neurofilament light (NfL) protein has particular interest, as its levels reflect neuroaxonal degeneration, a common feature in various neurodegenerative diseases. In the present study, we analyzed NfL levels in the CSF of 535 participants of the SPIN (Sant Pau Initiative on Neurodegeneration) cohort including cognitively normal participants, patients with Alzheimer disease (AD), Down syndrome (DS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We evaluated the differences in CSF NfL accross groups and its association with other CSF biomarkers and with cognitive scales. All neurogenerative diseases showed increased levels of CSF NfL, with the highest levels in patients with ALS, FTD, CBS and PSP. Furthermore, we found an association of CSF NfL levels with cognitive impairment in patients within the AD and FTD spectrum and with AD pathology in DLB and DS patients. These results have implications for the use of NfL as a marker in neurodegenerative diseases.

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Diagnostic and prognostic power of CSF Tau in amyotrophic lateral sclerosis

Cited by 32 publications

References 40 publications

Aβ1-42 and Tau as Potential Biomarkers for Diagnosis and Prognosis of Amyotrophic Lateral Sclerosis

Aβ1-42 and Tau as Potential Biomarkers for Diagnosis and Prognosis of Amyotrophic Lateral Sclerosis

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

Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders

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