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Alzheimers Dement. 2018 Jun;14(6):751-763. doi: 10.1016/j.jalz.2017.12.008. Epub 2018 Feb 3.

Cerebrospinal fluid neurofilament light levels in neurodegenerative dementia: Evaluation of diagnostic accuracy in the differential diagnosis of prion diseases.

Author information

1
Department of Neurology, University Medical School, Göttingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
2
Department of Epidemiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
3
Department of Neurology, University Medical School, Göttingen, Germany.
4
Laboratory of Pharmacology, School of Health Sciences, Department of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece.
5
Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland.
6
Network Center for Biomedical Research in Neurodegenerative Diseases, (CIBERNED), Institute Carlos III, Ministry of Health, Hospitalet de Llobregat, Barcelona, Spain.
7
Neurology Department, CHUC-Centro Hospitalar e Universitário de Coimbra, CNC- Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
8
Network Center for Biomedical Research in Neurodegenerative Diseases, (CIBERNED), Institute Carlos III, Ministry of Health, Hospitalet de Llobregat, Barcelona, Spain; Senior Consultant, Bellvitge University Hospital-IDIBELL, Department of Pathology and Experimental Therapeutics, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain.
9
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; UK Dementia Research Institute, London, UK.
10
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
11
Network Center for Biomedical Research in Neurodegenerative Diseases, (CIBERNED), Institute Carlos III, Ministry of Health, Hospitalet de Llobregat, Barcelona, Spain; Alzheimer Disease Research Unit, CIEN Foundation; Queen Sofia Foundation Alzheimer Center; Chronic Disease Programme Carlos III Institute of Health, Madrid, Spain.
12
Department of Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
13
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
14
Network Center for Biomedical Research in Neurodegenerative Diseases, (CIBERNED), Institute Carlos III, Ministry of Health, Hospitalet de Llobregat, Barcelona, Spain. Electronic address: franc.llorens@gmail.com.

Abstract

INTRODUCTION:

Neurofilament light (NFL) levels in the cerebrospinal fluid are increased in several neurodegenerative dementias. However, their diagnostic accuracy in the differential diagnostic context is unknown.

METHODS:

Cerebrospinal fluid NFL levels were quantified in nonprimarily neurodegenerative neurological and psychiatric diseases (n = 122), mild cognitive impairment (n = 48), Alzheimer's disease (n = 108), dementia with Lewy bodies/Parkinson's disease dementia (n = 53), vascular dementia (n = 46), frontotemporal dementia (n = 41), sporadic Creutzfeldt-Jakob disease (sCJD, n = 132), and genetic prion diseases (n = 182).

RESULTS:

The highest NFL levels were detected in sCJD, followed by vascular dementia, frontotemporal dementia, dementia with Lewy bodies/Parkinson's disease dementia, Alzheimer's disease, and mild cognitive impairment. In sCJD, NFL levels correlated with cerebrospinal fluid tau and disease duration. NFL levels were able to differentiate sCJD from nonprimarily neurodegenerative neurological and psychiatric diseases (area under the curve = 0.99, 95% confidence interval: 0.99-1) and from the other diagnostic groups showing cognitive impairment/dementia of a non-CJD etiology (area under the curve = 0.90, 95% confidence interval: 0.87-0.92). Compared to nonprimarily neurodegenerative neurological and psychiatric diseases, NFL was also elevated in genetic prion diseases associated with the E200K, V210I, P102L, and D178N prion protein gene mutations.

DISCUSSION:

Increased NFL levels are a common feature in neurodegenerative dementias.

KEYWORDS:

Alzheimer's disease; Cerebrospinal fluid; Dementia with Lewy bodies; Frontotemporal dementia; Neurodegenerative dementias; Neurofilament light; Parkinson's disease dementia; Prion diseases; Vascular dementia

PMID:
29391125
DOI:
10.1016/j.jalz.2017.12.008

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