title: Beta-amyloid and phosphorylated tau metabolism changes in narcolepsy over time.
abstract: OBJECTIVE
  The aim od this study is to test whether metabolism of beta-amyloid and tau proteins changes in narcolepsy along with the disease course.
  
  
  METHODS
  We analyzed a population of narcoleptic drug-naïve patients compared to a sample of healthy controls. Patients and controls underwent lumbar puncture for assessment of cerebrospinal fluid (CSF) beta-amyloid1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) levels. Moreover, based on the median disease duration of the whole narcolepsy group, the patients were divided into two subgroups: patients with a short disease duration (SdN, <5 years) and patients with a long disease duration (LdN, >5 years).
  
  
  RESULTS
  We found significantly lower CSF Aβ42 levels in the whole narcolepsy group with respect to controls. Taking into account the patient subgroups, we documented reduced CSF Aβ42 levels in SdN compared to both LdN and controls. Even LdN patients showed lower CSF Aβ42 levels with respect to controls. Moreover, we documented higher CSF p-tau levels in LdN patients compared to both SdN and controls. Finally, a significant positive correlation between CSF Aβ42 levels and disease duration was evident.
  
  
  CONCLUSIONS
  We hypothesize that beta-amyloid metabolism and cascade may be impaired in narcolepsy not only at the onset but also along with the disease course, although they show a compensatory profile over time. Concurrently, also CSF biomarkers indicative of neural structure (p-tau) appear to be altered in narcolepsy patients with a long disease duration. However, the mechanism underlying beta-amyloid and tau metabolism impairment in narcolepsy remains still unclear and deserves to be better elucidated.
authors.affiliation: Department of Systems Medicine, Neurophysiopathology Unit, Sleep Medicine Centre, University of Rome 'Tor Vergata', Viale Oxford 81, 00133, Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Liguori
authors.affiliation: Department of Systems Medicine, Neurophysiopathology Unit, Sleep Medicine Centre, University of Rome 'Tor Vergata', Viale Oxford 81, 00133, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Placidi
authors.affiliation: Department of Systems Medicine, Neurophysiopathology Unit, Sleep Medicine Centre, University of Rome 'Tor Vergata', Viale Oxford 81, 00133, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Izzi
authors.affiliation: Clinical Biochemistry and Molecular Biology, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Nuccetelli
authors.affiliation: Clinical Biochemistry and Molecular Biology, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.affiliation: Department of Systems Medicine, Neurophysiopathology Unit, Sleep Medicine Centre, University of Rome 'Tor Vergata', Viale Oxford 81, 00133, Rome, Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Sarpa
authors.affiliation: Department of Systems Medicine, Neurophysiopathology Unit, Sleep Medicine Centre, University of Rome 'Tor Vergata', Viale Oxford 81, 00133, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Cum
authors.affiliation: Department of Systems Medicine, Neurology Unit, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Marciani
authors.affiliation: Department of Systems Medicine, Neurophysiopathology Unit, Sleep Medicine Centre, University of Rome 'Tor Vergata', Viale Oxford 81, 00133, Rome, Italy.|Fondazione Santa Lucia IRCCS, Rome, Italy.
authors.forename: Nicola Biagio
authors.initials: NB
authors.lastname: Mercuri
authors.affiliation: Department of Systems Medicine, Neurophysiopathology Unit, Sleep Medicine Centre, University of Rome 'Tor Vergata', Viale Oxford 81, 00133, Rome, Italy. a_romigi@inwind.it.|IRCCS Neuromed, Via Atinense 18, 86077, Pozzilli, IS, Italy. a_romigi@inwind.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Romigi
mesh_terms: D000328:Adult; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D000068797:Orexins / Q000134:cerebrospinal fluid; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D017286:Polysomnography; D012016:Reference Values; D013129:Spinal Puncture; D013223:Statistics as Topic; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; C054369:MAPT protein, human; D000068797:Orexins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Beta-amyloid1–42; CSF; Narcolepsy; Orexin; Tau protein