Increased cerebrospinal fluid levels of nerve cell biomarkers in narcolepsy with cataplexy.
BACKGROUND
The association between narcolepsy with cataplexy and the hypocretinergic system in the central nervous system is strong since up to 75-90% of all patients have cerebrospinal fluid (CSF) hypocretin-1 deficiency. The predominant occurrence of HLADQB1*0602 tissue type in narcolepsy patients and recent results from genome-wide association studies suggest an underlying immunological mechanism. The present study was initiated to clarify whether measurement of nerve cell biomarkers in CSF could give additional knowledge of the pathophysiological mechanisms causing narcolepsy with cataplexy.


METHODS
Two patient groups with narcolepsy, comprising 18 patients with low CSF hypocretin-1 concentrations and typical cataplexy, and 18 patients with normal CSF hypocretin-1 levels and mild cataplexy-like symptoms, were compared to 17 controls. We measured the nerve cell biomarkers beta-amyloid (Aβ42), total tau protein (T-tau), phosphorylated tau (P-tau) and neuron-specific enolase (NSE) in CSF.


RESULTS
The concentrations of all biomarkers were significantly elevated in both patient groups compared to the controls. The concentration of beta-amyloid was significantly higher in the patient group with normal CSF hypocretin-1 concentration than in those with low concentrations, whereas the other biomarkers showed no difference between the patient groups.


CONCLUSIONS
The findings of elevated levels of CSF biomarkers independent of CSF hypocretin-1 reduction may reflect alterations in cell metabolism. The results suggest a more extensive affection of the sleep regulating cellular network, affecting other neuronal sites important in the regulation of sleep, in addition to the hypocretin-producing neurons.
Norwegian Resource Center for AD/HD, Tourette's Syndrome and Narcolepsy, Oslo University Hospital, Oslo, Norway. Electronic address: msheier@online.no.
M S
MS
Heier
Department of Multidisciplinary Laboratory Medicine and Medical Biochemistry, Akershus University Hospital, Lørenskog, Norway.
A
A
Skinningsrud
Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
E
E
Paus
Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
K M
KM
Gautvik
D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000134:cerebrospinal fluid*; D009479:Neuropeptides / Q000134:cerebrospinal fluid; D000068797:Orexins; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid; D055815:Young Adult; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D016875:tau Proteins; D010751:Phosphopyruvate Hydratase
Amyloid; Cataplexy; Enolase; Hypocretin; Narcolepsy; Tau proteins