TY - JOUR
T1 - Cerebrospinal Fluid Biomarkers of Neurodegeneration Are Decreased or Normal in Narcolepsy
AU - Jørgen Jennum, Poul
AU - Østergaard Pedersen, Lars
AU - Czarna Bahl, Justyna Maria
AU - Modvig, Signe
AU - Fog, Karina
AU - Holm, Anja
AU - Rahbek Kornum, Birgitte
AU - Gammeltoft, Steen
N1 - © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail [email protected].
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Objectives: 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. Methods: 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). Results: 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. Conclusion: 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.
AB - Objectives: 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. Methods: 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). Results: 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. Conclusion: 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.
KW - Adult
KW - Amyloid beta-Peptides/cerebrospinal fluid
KW - Biomarkers/cerebrospinal fluid
KW - Case-Control Studies
KW - Chitinase-3-Like Protein 1/cerebrospinal fluid
KW - Female
KW - Humans
KW - Hypersomnolence, Idiopathic/cerebrospinal fluid
KW - Male
KW - Narcolepsy/cerebrospinal fluid
KW - Neurodegenerative Diseases/cerebrospinal fluid
KW - Neurofilament Proteins/cerebrospinal fluid
KW - Orexins/cerebrospinal fluid
KW - alpha-Synuclein/cerebrospinal fluid
KW - tau Proteins/cerebrospinal fluid
U2 - 10.1093/sleep/zsw006
DO - 10.1093/sleep/zsw006
M3 - Journal article
C2 - 28364448
SN - 0161-8105
VL - 40
JO - Sleep
JF - Sleep
IS - 1
M1 - zsw006
ER -