Significance of CSF NfL and tau in ALS

被引：54

作者：

Schreiber, Stefanie ^{[1
,2
]}

Spotorno, Nicola ^{[2
]}

Schreiber, Frank ^{[1
,2
,3
]}

Acosta-Cabronero, Julio ^{[2
,4
]}

Kaufmann, Joern ^{[1
]}

Machts, Judith ^{[1
,2
]}

Debska-Vielhaber, Grazyna ^{[1
]}

Garz, Cornelia ^{[1
,2
]}

Bittner, Daniel ^{[1
,2
]}

Hensiek, Nathalie ^{[1
]}

Dengler, Reinhard ^{[5
]}

Petri, Susanne ^{[5
]}

Nestor, Peter J. ^{[2
,6
]}

Vielhaber, Stefan ^{[1
,2
]}

机构：

[1] Otto von Guericke Univ, Dept Neurol, Leipziger Str 44, D-39120 Magdeburg, Germany

[2] Helmholtz Assoc, German Ctr Neurodegenerat Dis DZNE, Leipziger Str 44, D-39120 Magdeburg, Germany

[3] Tech Univ Carolo Wilhelmina Braunschweig, Inst Control Engn, Hans Sommer Str 66, D-38106 Braunschweig, Germany

[4] UCL, UCL Inst Neurol, Wellcome Ctr Human Neuroimaging, London, England

[5] Hannover Med Sch, Dept Neurol, Carl Neuberg Str 1, D-30625 Hannover, Germany

[6] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia

来源：

JOURNAL OF NEUROLOGY | 2018年 / 265卷 / 11期

关键词：

Amyotrophic lateral sclerosis; MRI; Cerebrospinal fluid; Diffusion tensor imaging; Neurofilament light chain; Ttau; Tau phosphorylated at threonine 181 (ptau); Ptau/ttau ratio; AMYOTROPHIC-LATERAL-SCLEROSIS; NEUROFILAMENT LIGHT-CHAIN; CEREBROSPINAL-FLUID TAU; PROGNOSTIC BIOMARKER; CANDIDATE BIOMARKER; PHOSPHORYLATED TAU; DAMAGE MARKERS; MOTOR CORTEX; HEAVY-CHAIN; DISEASE;

D O I：

10.1007/s00415-018-9043-0

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：2633 / 2645

页数：13

共 65 条

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