CSF beta-amyloid levels are altered in narcolepsy: a link with the inflammatory hypothesis?

Abstract

Narcolepsy is characterized by hypocretin deficiency due to the loss of hypothalamic orexinergic neurons, and is associated with both the human leucocyte antigen DQB1*06:02 and the T cell receptor polymorphism. The above relationship suggests autoimmune/inflammatory processes underlying the loss of orexinergic neurons in narcolepsy. To test the autoimmune/inflammatory hypothesis by means of cerebrospinal fluid (CSF) levels of beta-amyloid1-42 and/or total tau proteins in a sample of narcoleptic patients, we analysed 16 narcoleptic patients and 16 healthy controls. Beta-amyloid1-42 CSF levels were significantly lower in narcoleptic patients compared with healthy controls. We also documented pathologically low levels of CSF beta-amyloid1-42 (<500 pg mL(-1) ) in six of 16 narcoleptic patients (37.5%). We hypothesize that the significant decrease of the CSF beta-amyloid1-42 levels in narcoleptic patients may support both the inflammatory/autoimmune hypothesis as the basis of the pathogenesis of narcolepsy and the prevalence of an 'amyloidogenic' pathway caused by the deficiency of the alpha-secretases enzymes.

• Authors: Claudio Liguori, Fabio Placidi, Maria Albanese, Marzia Nuccetelli, Francesca Izzi, Maria Grazia Marciani, Nicola Biagio Mercuri, Sergio Bernardini, Andrea Romigi
• Journal: Journal of sleep research (J Sleep Res) Vol. 23 Issue 4 Pg. 420-4 (Aug 2014) ISSN: 1365-2869 [Electronic] England
• PMID: 24635662 (Publication Type: Journal Article)
• Copyright: © 2014 European Sleep Research Society.

Chemical References

• Amyloid beta-Peptides
• Intracellular Signaling Peptides and Proteins
• Neuropeptides
• Orexins
• Peptide Fragments
• amyloid beta-protein (1-42)
• tau Proteins

Topics

• Adolescent
• Adult
• Amyloid beta-Peptides (cerebrospinal fluid)
• Case-Control Studies
• Female
• Humans
• Inflammation (cerebrospinal fluid, metabolism)
• Intracellular Signaling Peptides and Proteins (analysis)
• Male
• Middle Aged
• Models, Biological
• Narcolepsy (cerebrospinal fluid, metabolism, pathology)
• Neuropeptides (analysis)
• Orexins
• Peptide Fragments (cerebrospinal fluid)
• Phosphorylation
• Young Adult
• tau Proteins (cerebrospinal fluid, metabolism)