Skip to main content

Advertisement

SpringerLink
Log in

Beta-amyloid and phosphorylated tau metabolism changes in narcolepsy over time

  • Neurology • Original Article
  • Published:
Sleep and Breathing Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. International Classification of Sleep Disorders (2014) Darien, Ill.: American Academy of Sleep Medicine

  2. Dauvilliers Y, Billiard M, Montplaisir J (2003) Clinical aspects and pathophysiology of narcolepsy. Clin Neurophysiol 114:2000–2017

    Article  PubMed  Google Scholar 

  3. Overeem S, Mignot E, van Dijk JG, Lammers GJ (2001) Narcolepsy: clinical features, new pathophysiologic insights, and future perspectives. J Clin Neurophysiol 18:78–105

    Article  CAS  PubMed  Google Scholar 

  4. Thannickal TC, Moore RY, Nienhuis R et al (2000) Reduced number of hypocretin neurons in human narcolepsy. Neuron 27:469–474

    Article  CAS  PubMed  Google Scholar 

  5. Mignot E, Lammers GJ, Ripley B et al (2002) The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol 59:1553–1562

    Article  PubMed  Google Scholar 

  6. Kornum BR, Faraco J, Mignot E (2011) Narcolepsy with hypocretin/orexin deficiency, infections and autoimmunity of the brain. Curr Opin Neurobiol 21(6):897–903

    Article  CAS  PubMed  Google Scholar 

  7. Partinen M, Kornum BR, Plazzi G, Jennum P, Julkunen I, Vaarala O (2014) Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination. Lancet Neurol 13(6):600–613

    Article  CAS  PubMed  Google Scholar 

  8. Kallweit U, Hidalgo H, Engel A, Baumann CR, Bassetti CL, Dahmen N (2012) Post H1N1 vaccination narcolepsy-cataplexy with decreased CSF beta-amyloid. Sleep Med 13(3):323

    Article  PubMed  Google Scholar 

  9. Liguori C, Placidi F, Albanese M et al (2014) CSF beta-amyloid are altered in narcolepsy: a link with the inflammatory hypothesis? Sleep Res 23(4):420–424

    Article  Google Scholar 

  10. Heier MS, Skinningsrud A, Paus E, Gautvik KM (2014) Increased cerebrospinal fluid levels of nerve cell biomarkers in narcolepsy with cataplexy. Sleep Med 15(6):614–618

    Article  CAS  PubMed  Google Scholar 

  11. Dauvilliers YA, Lehmann S, Jaussent I, Gabelle A (2014) Hypocretin and brain β-amyloid peptide interactions in cognitive disorders and narcolepsy. Front Aging Neurosci 6:119

    Article  PubMed  PubMed Central  Google Scholar 

  12. Liguori C, Placidi F, Izzi F et al (2014) May CSF beta-amyloid and tau proteins levels be influenced by long treatment duration and stable medication in narcolepsy? Sleep Med 15(11):1424

    Article  PubMed  Google Scholar 

  13. Sancesario GM, Esposito Z, Nuccetelli M et al (2010) Abeta1-42 detection in CSF of Alzheimer’s disease is influenced by temperature: indication of reversible Abeta1-42 aggregation? Exp Neurol 223(2):371–376

    Article  CAS  PubMed  Google Scholar 

  14. Liguori C, Romigi A, Mercuri NB et al (2014) Cerebrospinal-fluid orexin levels and daytime somnolence in frontotemporal dementia. J Neurol 261(9):1832–1836

    Article  CAS  PubMed  Google Scholar 

  15. Fontana A, Gast H, Reith W, Recher M, Birchler T, Bassetti CL (2010) Narcolepsy: autoimmunity, effector T cell activation due to infection, or T cell independent, major histocompatibility complex class II induced neuronal loss? Brain 133:1300–1311

    Article  PubMed  Google Scholar 

  16. Miyagawa T, Miyadera H, Tanaka S et al (2011) Abnormally low serum acylcarnitine levels in narcolepsy patients. Sleep 34:349–353

    PubMed  PubMed Central  Google Scholar 

  17. Miyagawa T, Kawamura H, Obuchi M et al (2013) Effects of oral L-carnitine administration in narcolepsy patients: a randomized, double-blind, cross-over and placebo-controlled trial. PLoS One 8:e53707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Romigi A, Liguori C, Izzi F et al (2015) Oral l-carnitine as treatment for narcolepsy without cataplexy during pregnancy: a case report. J Neurol Sci 348(1–2):282–283

    Article  PubMed  Google Scholar 

  19. Liguori C, Dinallo V, Pieri M, et al. (2015) MicroRNA expression is dysregulated in narcolepsy: a new evidence? Sleep Med 16(8):1027–1028

  20. Hickman SE, Allison EK, El Khoury J (2008) Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer’s disease mice. J Neurosci 28(33):8354–8360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Soscia SJ, Kirby JE, Washicosky KJ et al (2010) The Alzheimer’s disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One 5(3):e9505

    Article  PubMed  PubMed Central  Google Scholar 

  22. Aran A, Lin L, Nevsimalova S et al (2009) Elevated anti-streptococcal antibodies in patients with recent narcolepsy onset. Sleep 32(8):979–983

    PubMed  PubMed Central  Google Scholar 

  23. Han F, Lin L, Li J et al (2012) TCRA, P2RY11, and CPT1B/CHKB associations in Chinese narcolepsy. Sleep Med 13(3):269–272

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kornum BR, Pizza F, Knudsen S, Plazzi G, Jennum P, Mignot E (2015) Cerebrospinal fluid cytokine levels in type 1 narcolepsy patients very close to onset. Brain Behav Immun 49:54–58

  25. Dauvilliers Y, Jaussent I, Lecendreux M et al (2014) Cerebrospinal fluid and serum cytokine profiles in narcolepsy with cataplexy: a case–control study. Brain Behav Immun 37:260–266

    Article  CAS  PubMed  Google Scholar 

  26. De Strooper B, Vassar R, Golde T (2010) The secretases: enzymes with therapeutic potential in Alzheimer disease. Nat Rev Neurol 6:99–107

    Article  PubMed  PubMed Central  Google Scholar 

  27. Honda M, Arai T, Fukazawa M et al (2009) Absence of ubiquitinated inclusions in hypocretin neurons of patients with narcolepsy. Neurology 73:511–517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Economou NT, Manconi M, Ghika J, Raimondi M, Bassetti CL (2012) Development of Parkinson and Alzheimer diseases in two cases of narcolepsy-cataplexy. Eur Neurol 67(1):48–50

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Systems Medicine, Neurophysiopathology Unit, Sleep Medicine Centre, University of Rome ‘Tor Vergata’, Viale Oxford 81, 00133, Rome, Italy

    Claudio Liguori, Fabio Placidi, Francesca Izzi, Maria Giovanna Sarpa, Fabrizio Cum, Nicola Biagio Mercuri & Andrea Romigi

  2. Clinical Biochemistry and Molecular Biology, University of Rome ‘Tor Vergata’, Rome, Italy

    Marzia Nuccetelli & Sergio Bernardini

  3. Department of Systems Medicine, Neurology Unit, University of Rome ‘Tor Vergata’, Rome, Italy

    Maria Grazia Marciani

  4. Fondazione Santa Lucia IRCCS, Rome, Italy

    Nicola Biagio Mercuri

  5. IRCCS Neuromed, Via Atinense 18, 86077, Pozzilli, IS, Italy

    Andrea Romigi

Authors
  1. Claudio Liguori
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fabio Placidi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francesca Izzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marzia Nuccetelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sergio Bernardini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maria Giovanna Sarpa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fabrizio Cum
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Maria Grazia Marciani
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nicola Biagio Mercuri
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Andrea Romigi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea Romigi.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Comments

In this manuscript, the authors evaluated the levels of CSF biomarkers in drug-naïve narcoleptic patients using enzyme-linked immunosorbent assays. The CSF samples were collected from 26 narcoleptic patients (SDN < 5 years, n = 13; and LDN < 5 years, n = 13) and 17 healthy controls. The results demonstrated that while CSF levels of Aβ42 were significantly decreased in SDN and LDN compared to the control, its levels were lower in SDN compared to LDN. They also reported a significant positive correlation between the CSF levels of Aβ42 and disease duration. Further, they detected an increase in the level of p-tau in LDN compared to SDN and control, and no differences in the level of t-tau across the three groups. The authors concluded impairment in Aβ42 metabolism at the onset and along the disease course.

Overall, the aim of this study is clear and addressing an important clinical point in narcolepsy.

Sausan Azzam

Ohio, USA

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liguori, C., Placidi, F., Izzi, F. et al. Beta-amyloid and phosphorylated tau metabolism changes in narcolepsy over time. Sleep Breath 20, 277–283 (2016). https://doi.org/10.1007/s11325-015-1305-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11325-015-1305-9

Keywords

Search

Navigation