Cerebrospinal Fluid Biomarkers of Neurodegeneration Are Decreased or Normal in Narcolepsy

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 beta-amyloid, total tau protein (T-tau), phosphorylated tau protein (P-tau181), a-synuclein, neurofilament light chain (NF-L), and chitinase 3-like protein-1 (CHI3L1). Results: Levels of beta-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 a-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 beta-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.