Inga Zerr1, Matthias Schmitz1, André Karch2, Anna Villar-Piqué3, Eirini Kanata4, Ewa Golanska5, Daniela Díaz-Lucena6, Aikaterini Karsanidou4, Peter Hermann3, Tobias Knipper3, Stefan Goebel3, Daniela Varges3, Theodoros Sklaviadis4, Beata Sikorska5, Pawel P Liberski5, Isabel Santana7, Isidro Ferrer8, Henrik Zetterberg9, Kaj Blennow10, Olga Calero11, Miguel Calero11, Anna Ladogana12, Raquel Sánchez-Valle13, Inês Baldeiras7, Franc Llorens14. 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.
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 D178Nprion protein gene mutations. DISCUSSION: Increased NFL levels are a common feature in neurodegenerative dementias.
Authors: Anna Villar-Piqué; Matthias Schmitz; Ingolf Lachmann; André Karch; Olga Calero; Christiane Stehmann; Shannon Sarros; Anna Ladogana; Anna Poleggi; Isabel Santana; Isidre Ferrer; Eva Mitrova; Dana Žáková; Maurizio Pocchiari; Inês Baldeiras; Miguel Calero; Steven J Collins; Michael D Geschwind; Raquel Sánchez-Valle; Inga Zerr; Franc Llorens Journal: Mol Neurobiol Date: 2018-07-30 Impact factor: 5.590
Authors: Matthias Schmitz; Sezgi Canaslan; Juan Carlos Espinosa; Natalia Fernández-Borges; Anna Villar-Piqué; Franc Llorens; Daniela Varges; Fabian Maass; Juan Maria Torres; Peter Hermann; Inga Zerr Journal: Mol Neurobiol Date: 2022-06-18 Impact factor: 5.682
Authors: Francesco Panza; Bruno P Imbimbo; Madia Lozupone; Davide Seripa; Antonio Daniele; Mark Watling; Gianluigi Giannelli Journal: Nat Rev Neurol Date: 2020-03-23 Impact factor: 42.937
Authors: Peter Hermann; Brian Appleby; Jean-Philippe Brandel; Byron Caughey; Steven Collins; Michael D Geschwind; Alison Green; Stephane Haïk; Gabor G Kovacs; Anna Ladogana; Franc Llorens; Simon Mead; Noriyuki Nishida; Suvankar Pal; Piero Parchi; Maurizio Pocchiari; Katsuya Satoh; Gianluigi Zanusso; Inga Zerr Journal: Lancet Neurol Date: 2021-03 Impact factor: 44.182