| Title |
Significance of CSF NfL and tau in ALS
|
|---|---|
| Published in |
Journal of Neurology, September 2018
|
| DOI | 10.1007/s00415-018-9043-0 |
| Pubmed ID | |
| Authors |
Stefanie Schreiber, Nicola Spotorno, Frank Schreiber, Julio Acosta-Cabronero, Jörn Kaufmann, Judith Machts, Grazyna Debska-Vielhaber, Cornelia Garz, Daniel Bittner, Nathalie Hensiek, Reinhard Dengler, Susanne Petri, Peter J. Nestor, Stefan Vielhaber |
| Abstract |
Cerebrospinal fluid (CSF) neurofilament light chain (NfL) has emerged as putative diagnostic biomarker in amyotrophic lateral sclerosis (ALS), but it remains a matter of debate, whether CSF total tau (ttau), tau phosphorylated at threonine 181 (ptau) and the ptau/ttau ratio could serve as diagnostic biomarker in ALS as well. Moreover, the relationship between CSF NfL and tau measures to further axonal and (neuro)degeneration markers still needs to be elucidated. Our analysis included 89 ALS patients [median (range) age 63 (33-83) years, 61% male, disease duration 10 (0.2-190) months] and 33 age- and sex-matched disease controls [60 (32-76), 49%]. NfL was higher and the ptau/ttau ratio was lower in ALS compared to controls [8343 (1795-35,945) pg/ml vs. 1193 (612-2616), H(1) = 70.8, p < 0.001; mean (SD) 0.17 (0.04) vs. 0.2 (0.03), F(1) = 14.3, p < 0.001], as well as in upper motor neuron dominant (UMND, n = 10) compared to classic (n = 46) or lower motor neuron dominant ALS [n = 31; for NfL: 16,076 (7447-35,945) vs. 8205 (2651-35,138) vs. 8057 (1795-34,951)], Z ≥ 2.5, p ≤ 0.01; for the ptau/ttau ratio: [0.13 (0.04) vs. 0.17 (0.04) vs. 0.18 (0.03), p ≤ 0.02]. In ALS, NfL and the ptau/ttau ratio were related to corticospinal tract (CST) fractional anisotropy (FA) and radial diffusivity (ROI-based approach and whole-brain voxelwise analysis). Factor analysis of mixed data revealed a co-variance pattern between NfL (factor load - 0.6), the ptau/ttau ratio (0.7), CST FA (0.8) and UMND ALS phenotype (- 2.8). NfL did not relate to any further neuroaxonal injury marker (brain volumes, precentral gyrus thickness, peripheral motor amplitudes, sonographic cross-sectional nerve area), but a lower ptau/ttau ratio was associated with whole-brain gray matter atrophy and widespread white matter integrity loss. Higher NfL baseline levels were associated with greater UMN disease burden, more rapid disease progression, a twofold to threefold greater hazard of death and shorter survival times. The findings that higher CSF NfL levels and a reduced ptau/ttau ratio are more associated with clinical UMN involvement and with reduced CST FA offer strong converging evidence that both are markers of central motor degeneration. Furthermore, NfL is a marker of poor prognosis, while a low ptau/ttau ratio indicates extramotor pathology in ALS. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 20% |
| Australia | 1 | 20% |
| Unknown | 3 | 60% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 85 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 85 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 17 | 20% |
| Student > Ph. D. Student | 13 | 15% |
| Student > Master | 11 | 13% |
| Student > Bachelor | 7 | 8% |
| Student > Postgraduate | 6 | 7% |
| Other | 7 | 8% |
| Unknown | 24 | 28% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 19 | 22% |
| Medicine and Dentistry | 10 | 12% |
| Biochemistry, Genetics and Molecular Biology | 6 | 7% |
| Agricultural and Biological Sciences | 3 | 4% |
| Nursing and Health Professions | 2 | 2% |
| Other | 12 | 14% |
| Unknown | 33 | 39% |
Attention Score in Context
This research output has an Altmetric Attention Score of 12. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 September 2019.
All research outputs
#2,647,630
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Outputs from Journal of Neurology
#519
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#55,898
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Outputs of similar age from Journal of Neurology
#15
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