Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases

被引：261

作者：

Bacioglu, Mehtap ^{[1
,2
,3
]}

Maia, Luis F. ^{[1
,2
,4
]}

Preische, Oliver ^{[1
,5
]}

Schelle, Juliane ^{[1
,2
,3
]}

Apel, Anja ^{[1
,6
]}

Kaeser, Stephan A. ^{[1
,2
]}

Schweighauser, Manuel ^{[1
,2
,3
]}

Eninger, Timo ^{[1
,2
,3
]}

Lambert, Marius ^{[1
,2
]}

Pilotto, Andrea ^{[1
,6
]}

Shimshek, Derya R. ^{[7
]}

Neumann, Ulf ^{[7
]}

Kahle, Philipp J. ^{[1
,6
]}

Staufenbiel, Matthias ^{[1
,2
]}

Neumann, Manuela ^{[1
,8
]}

Maetzler, Walter ^{[1
,6
]}

Kuhle, Jens ^{[9
,10
,11
]}

Jucker, Mathias ^{[1
,2
]}

机构：

[1] German Ctr Neurodegenerat Dis DZNE, D-72076 Tubingen, Tuebingen, Germany

[2] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Cellular Neurol, D-72076 Tubingen, Germany

[3] Univ Tubingen, Grad Sch Cellular & Mol Neurosci, D-72074 Tubingen, Germany

[4] Hosp Santo Antonio CHP, Dept Neurol, P-4099001 Oporto, Portugal

[5] Univ Tubingen, Dept Psychiat & Psychotherapy, D-72076 Tubingen, Germany

[6] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat, D-72076 Tubingen, Germany

[7] Novartis Pharma AG, Novartis Inst BioMed Res, CH-4002 Basel, Switzerland

[8] Univ Tubingen, Dept Neuropathol, D-72076 Tubingen, Germany

[9] Univ Basel Hosp, Dept Med, Neurol, CH-4031 Basel, Switzerland

[10] Univ Basel Hosp, Dept Biomed, Neurol, CH-4031 Basel, Switzerland

[11] Univ Basel Hosp, Dept Clin Res, Neurol, CH-4031 Basel, Switzerland

来源：

NEURON | 2016年 / 91卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

SUBUNIT PNF-H; TRANSGENIC MICE; CEREBROSPINAL-FLUID; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; PROGNOSTIC BIOMARKER; PARKINSONS-DISEASE; NERVOUS-SYSTEM; AXONOPATHY;

D O I：

10.1016/j.neuron.2016.05.018

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (alpha-synuclein, Tau, A beta). To monitor such treatments, fluid biomarkers reflecting the underlying disease process are crucial. We found robust increases of neurofilament light chain (NfL) in CSF and blood in murine models of alpha-synucleinopathies, tauopathy, and beta-amyloidosis. Blood and CSF NfL levels were strongly correlated, and NfL increases coincided with the onset and progression of the corresponding proteopathic lesions in brain. Experimental induction of alpha-synuclein lesions increased CSF and blood NfL levels, while blocking Ab lesions attenuated the NfL increase. Consistently, we also found NfL increases in CSF and blood of human alpha-synucleinopathies, tauopathies, and Alzheimer's disease. Our results suggest that CSF and particularly blood NfL can serve as a reliable and easily accessible biomarker to monitor disease progression and treatment response in mouse models and potentially in human proteopathic neurodegenerative diseases.

引用

页码：56 / 66

页数：11

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