title: 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.affiliation: Department of Systems Medicine, Neurophysiopathology Unit, Sleep Medicine Centre, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Liguori
authors.forename: Fabio
authors.initials: F
authors.lastname: Placidi
authors.forename: Maria
authors.initials: M
authors.lastname: Albanese
authors.forename: Marzia
authors.initials: M
authors.lastname: Nuccetelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Izzi
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Marciani
authors.forename: Nicola Biagio
authors.initials: NB
authors.lastname: Mercuri
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Andrea
authors.initials: A
authors.lastname: Romigi
mesh_terms: D000293:Adolescent; D000328:Adult; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000134:cerebrospinal fluid / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009290:Narcolepsy / Q000134:cerebrospinal fluid* / Q000378:metabolism / Q000473:pathology; D009479:Neuropeptides / Q000032:analysis; D000068797:Orexins; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D055815:Young Adult; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: CSF; beta-amyloid1-42; narcolepsy; orexin