Cerebrospinal Fluid Biomarkers of Neurodegeneration Are Decreased or Normal in Narcolepsy

• Published in: Sleep (New York, N.Y.) Vol. 40; no. 1
• Main Authors: Jennum, Poul Jørgen, Østergaard Pedersen, Lars, Czarna Bahl, Justyna Maria, Modvig, Signe, Fog, Karina, Holm, Anja, Rahbek Kornum, Birgitte, Gammeltoft, Steen
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.01.2017
• Subjects: Adult; alpha-Synuclein - cerebrospinal fluid; Amyloid beta-Peptides - cerebrospinal fluid; Biomarkers; Biomarkers - cerebrospinal fluid; Case-Control Studies; Chitinase-3-Like Protein 1 - cerebrospinal fluid; Female; Humans; Hypersomnolence, Idiopathic - cerebrospinal fluid; Male; Narcolepsy - cerebrospinal fluid; Neurodegeneration; Neurodegenerative Diseases - cerebrospinal fluid; Neurofilament Proteins - cerebrospinal fluid; Orexins - cerebrospinal fluid; Proteins; Sleep disorders; tau Proteins - cerebrospinal fluid; hypocretin; neurodegeneration; BDNF; narcolepsy; β-amyloid
• ISSN: 1550-9109; 0161-8105; 1550-9109
• DOI: 10.1093/sleep/zsw006

To investigate whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration are altered in narcolepsy in order to evaluate whether the hypocretin deficiency and abnormal sleep-wake pattern in narcolepsy leads to neurodegeneration. Twenty-one patients with central hypersomnia (10 type 1 narcolepsy, 5 type 2 narcolepsy, and 6 idiopathic hypersomnia cases), aged 33 years on average and with a disease duration of 2-29 years, and 12 healthy controls underwent CSF analyses of the levels of β-amyloid, total tau protein (T-tau), phosphorylated tau protein (P-tau181), α-synuclein, neurofilament light chain (NF-L), and chitinase 3-like protein-1 (CHI3L1). Levels of β-amyloid were lower in patients with type 1 narcolepsy (375.4 ± 143.5 pg/mL) and type 2 narcolepsy (455.9 ± 65.0 pg/mL) compared to controls (697.9 ± 167.3 pg/mL, p < .05). Furthermore, in patients with type 1 narcolepsy, levels of T-tau (79.0 ± 27.5 pg/mL) and P-tau181 (19.1 ± 4.3 pg/mL) were lower than in controls (162.2 ± 49.9 pg/mL and 33.8 ± 9.2 pg/mL, p < .05). Levels of α-synuclein, NF-L, and CHI3L1 in CSF from narcolepsy patients were similar to those of healthy individuals. Six CSF biomarkers of neurodegeneration were decreased or normal in narcolepsy indicating that taupathy, synucleinopathy, and immunopathy are not prevalent in narcolepsy patients with a disease duration of 2-29 years. Lower CSF levels of β-amyloid, T-tau protein, and P-tau181 in narcolepsy may indicate that hypocretin deficiency and an abnormal sleep-wake pattern alter the turnover of these proteins in the central nervous system.