title: Hypocretin in cerebrospinal fluid is positively correlated with Tau and pTau.
abstract: It has been suggested that sleep-wake regulation as well as hypocretins play a role in the pathophysiology of Alzheimer's disease. We analyzed Aβ40, Aβ42, Tau protein, phosphorylated Tau (pTau) protein as well as hypocretin-1 concentrations in the CSF of a detection sample of 10 patients with Alzheimer's disease (AD) as well as 10 age- and gender-matched patients with major depression as a comparison group of different pathology. In order to replicate the findings, we used a confirmation sample of 17 AD patients and 8 patients with major depression. We found hypocretin-1 concentrations in CSF not to differ between patients with depression and AD. However, hypocretin-1 was significantly related to Tau (r=0.463, p<0.001) and pTau (r=0.630, p<0.0001). These effects were more pronounced in depressed patients when compared to AD patients. We conclude that hypocretin-1 may play a role in the metabolism of Tau proteins across different diagnostic entities including AD. It has to be determined whether there is a causal relationship between hypocretin-1 and Tau as well as pTau.
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany. Electronic address: michael.deuschle@zi-mannheim.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Deuschle
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schilling
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany.
authors.forename: F Markus
authors.initials: FM
authors.lastname: Leweke
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Enning
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstrasse 10, 80804 München, Germany; Center of Mental Health Klinikum Ingolstadt, Krumenauerstraße 25, 85049 Ingolstadt, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pollmächer
authors.affiliation: LVR-Hospital Essen, Deparment of Psychiatry and Psychotherapy, Medical Faculty, University of Duisburg-Essen, Virchowstrasse 174, 45147 Essen, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Esselmann
authors.affiliation: LVR-Hospital Essen, Deparment of Psychiatry and Psychotherapy, Medical Faculty, University of Duisburg-Essen, Virchowstrasse 174, 45147 Essen, Germany; Dept. of Psychiatry and Psychotherapy, University of Göttingen, Von-Siebold-Str. 5, 37075 Göttingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Wiltfang
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Frölich
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany; Department of Psychiatry, Charite, Eschenalle 3, 14050 Berlin, Germany.
authors.forename: Isabella
authors.initials: I
authors.lastname: Heuser
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003865:Major Depressive Disorder / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000134:cerebrospinal fluid*; D000068797:Orexins; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer's disease; Aβ; Depression; Hypocretin; Orexin; Tau protein