title: Cerebrospinal fluid levels of orexin-A and histamine, and sleep profile within the Alzheimer process.
abstract: To better understand how sleep/wake dysregulation affects Alzheimer's disease (AD), we compared the cerebrospinal fluid (CSF) orexin and histamine/tele-methylhistamine (HA/t-MHA) levels of 82 patients (41 probable-AD-high level of evidence, 41 mild cognitive impairment MCI-due-to-AD), 24 other neurologic disorders (OND) and 24 controls. We determined the relationships between these biomarkers, the CSF AD biomarkers concentrations, and the clinical sleep profile. CSF orexin-A but not HA/t-MHA levels were higher in MCI and AD than OND and controls. CSF orexin-A is correlated to CSF amyloid-β42in MCI and AD, independently of age, gender, MMSE, total-tau/phosphorylated-tau, HA or sleep parameters. Nighttime sleep duration was longer in MCI and AD patients than controls. In MCI, nighttime sleep duration negatively correlated with CSF amyloid-β42and MMSE. To conclude, CSF orexin-A but not HA/t-HMA was upregulated in AD and correlated with amyloid-β42level. Our data suggested a change in the sleep-wake pattern at an early stage of the disease that needs further investigation to deeply explain the mechanistic interplay between sleep and Alzheimer.
authors.affiliation: Memory Research and Resources Center, Department of Neurology, Montpellier University Hospital, Montpellier, France; University of Montpellier, Montpellier, France; INSERM U1183 Biotherapy Research Institute of Montpellier, CHU Saint Eloi, Montpellier, France. Electronic address: a-gabelle@chu-montpellier.fr.
authors.forename: Audrey
authors.initials: A
authors.lastname: Gabelle
authors.affiliation: University of Montpellier, Montpellier, France; INSERM U1061, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Jaussent
authors.affiliation: University of Montpellier, Montpellier, France; INSERM U1183 Biotherapy Research Institute of Montpellier, CHU Saint Eloi, Montpellier, France; Laboratoire de Biochimie Protéomique Clinique, Montpellier, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Hirtz
authors.affiliation: University of Montpellier, Montpellier, France; INSERM U1183 Biotherapy Research Institute of Montpellier, CHU Saint Eloi, Montpellier, France; Laboratoire de Biochimie Protéomique Clinique, Montpellier, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Vialaret
authors.affiliation: Memory Research and Resources Center, Department of Neurology, Montpellier University Hospital, Montpellier, France; University of Montpellier, Montpellier, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Navucet
authors.affiliation: Memory Research and Resources Center, Department of Neurology, Montpellier University Hospital, Montpellier, France; University of Montpellier, Montpellier, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Grasselli
authors.affiliation: Bioprojet-Biotech, Saint Grégoire, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Robert
authors.affiliation: University of Montpellier, Montpellier, France; INSERM U1183 Biotherapy Research Institute of Montpellier, CHU Saint Eloi, Montpellier, France; Laboratoire de Biochimie Protéomique Clinique, Montpellier, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lehmann
authors.affiliation: University of Montpellier, Montpellier, France; INSERM U1061, Montpellier, France; Sleep Unit, Narcolepsy Reference Center, Department of Neurology, Gui de Chauliac Hospital, Montpellier, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Dauvilliers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000503:physiopathology; D005260:Female; D006632:Histamine / Q000134:cerebrospinal fluid*; D006801:Humans; D008297:Male; D008761:Methylhistamines / Q000134:cerebrospinal fluid; D008875:Middle Aged; D000068797:Orexins / Q000134:cerebrospinal fluid*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D012890:Sleep / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D008761:Methylhistamines; D000068797:Orexins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D006632:Histamine; C020404:tele-methylhistamine
keywords: Alzheimer; Amyloid; Histamine; Orexin; Sleep