Franc Llorens1, Niels Kruse2, Matthias Schmitz3, Nadine Gotzmann3, Ewa Golanska4, Katrin Thüne3, Orgeta Zejneli5, Eirini Kanata5, Tobias Knipper6, Maria Cramm3, Peter Lange6, Saima Zafar3, Beata Sikorska4, Pawel P Liberski4, Eva Mitrova7, Daniela Varges6, Christian Schmidt6, Theodoros Sklaviadis5, Brit Mollenhauer8, Inga Zerr3. 1. Department of Neurology, Clinical Dementia Center, University Medical Center Göttingen, Göttingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Site Göttingen, Germany. Electronic address: franc.llorens@gmail.com. 2. Institute for Neuropathology, University Medical Center Göttingen, Göttingen, Germany. 3. Department of Neurology, Clinical Dementia Center, University Medical Center Göttingen, Göttingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Site Göttingen, Germany. 4. Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland. 5. Laboratory of Pharmacology, School of Health Sciences, Department of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece. 6. Department of Neurology, Clinical Dementia Center, University Medical Center Göttingen, Göttingen, Germany. 7. Department of Prion Diseases, Slovak Medical University Bratislava, Bratislava, Slovakia. 8. Institute for Neuropathology, University Medical Center Göttingen, Göttingen, Germany; Paracelsus-Elena Klinik, Center for Parkinsonism and Movement Disorders, Kassel, Germany; Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany.
Abstract
INTRODUCTION: Accurate diagnosis of prion diseases and discrimination from alternative dementias gain importance in the clinical routine, but partial overlap in cerebrospinal fluid (CSF) biomarkers impedes absolute discrimination in the differential diagnostic context. METHODS: We established the clinical parameters for prion disease diagnosis for the quantification of CSF α-synuclein in patients with sporadic (n = 234) and genetic (n = 56) prion diseases, in cases with cognitive impairment/dementia or neurodegenerative disease (n = 278), and in the neurologic control group (n = 111). RESULTS: An optimal cutoff value of 680 pg/mL α-synuclein results in 94% sensitivity and 96% specificity when diagnosing sporadic Creutzfeldt-Jakob disease (CJD). Genetic CJD cases showed increased CSF α-synuclein values. No increased α-synuclein levels were detected in non-CJD cases with rapid progression course. DISCUSSION: Detection of α-synuclein in the CSF of patients with suspected CJD is a valuable diagnostic test reaching almost full discrimination from non-prion disease cases. These data highlight the utility of CSF α-synuclein quantification in front of classical CSF biomarkers in clinical routine.
INTRODUCTION: Accurate diagnosis of prion diseases and discrimination from alternative dementias gain importance in the clinical routine, but partial overlap in cerebrospinal fluid (CSF) biomarkers impedes absolute discrimination in the differential diagnostic context. METHODS: We established the clinical parameters for prion disease diagnosis for the quantification of CSF α-synuclein in patients with sporadic (n = 234) and genetic (n = 56) prion diseases, in cases with cognitive impairment/dementia or neurodegenerative disease (n = 278), and in the neurologic control group (n = 111). RESULTS: An optimal cutoff value of 680 pg/mL α-synuclein results in 94% sensitivity and 96% specificity when diagnosing sporadic Creutzfeldt-Jakob disease (CJD). Genetic CJD cases showed increased CSF α-synuclein values. No increased α-synuclein levels were detected in non-CJD cases with rapid progression course. DISCUSSION: Detection of α-synuclein in the CSF of patients with suspected CJD is a valuable diagnostic test reaching almost full discrimination from non-prion disease cases. These data highlight the utility of CSF α-synuclein quantification in front of classical CSF biomarkers in clinical routine.
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: 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