Claudio Liguori1, Fabio Placidi1, Francesca Izzi1, Marzia Nuccetelli2, Sergio Bernardini2, Maria Giovanna Sarpa1, Fabrizio Cum1, Maria Grazia Marciani3, Nicola Biagio Mercuri1,4, Andrea Romigi5,6. 1. Department of Systems Medicine, Neurophysiopathology Unit, Sleep Medicine Centre, University of Rome 'Tor Vergata', Viale Oxford 81, 00133, Rome, Italy. 2. Clinical Biochemistry and Molecular Biology, University of Rome 'Tor Vergata', Rome, Italy. 3. Department of Systems Medicine, Neurology Unit, University of Rome 'Tor Vergata', Rome, Italy. 4. Fondazione Santa Lucia IRCCS, Rome, Italy. 5. Department of Systems Medicine, Neurophysiopathology Unit, Sleep Medicine Centre, University of Rome 'Tor Vergata', Viale Oxford 81, 00133, Rome, Italy. a_romigi@inwind.it. 6. IRCCS Neuromed, Via Atinense 18, 86077, Pozzilli, IS, Italy. a_romigi@inwind.it.
Abstract
PURPOSE: 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.
PURPOSE: 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 narcolepsypatients 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.
Entities:
Keywords:
Beta-amyloid1–42; CSF; Narcolepsy; Orexin; Tau protein
Authors: Ulf Kallweit; Hildegard Hidalgo; Alice Engel; Christian R Baumann; Claudio L Bassetti; Norbert Dahmen Journal: Sleep Med Date: 2011-12-14 Impact factor: 3.492
Authors: C Liguori; A Romigi; N B Mercuri; M Nuccetelli; F Izzi; M Albanese; G Sancesario; A Martorana; G M Sancesario; S Bernardini; M G Marciani; F Placidi Journal: J Neurol Date: 2014-08-14 Impact factor: 4.849
Authors: Andrea Romigi; Giuseppe Vitrani; Temistocle Lo Giudice; Diego Centonze; Valentina Franco Journal: Drug Des Devel Ther Date: 2018-08-30 Impact factor: 4.162