title: Measuring Compounds in Exhaled Air to Detect Alzheimer's Disease and Parkinson's Disease.
abstract: BACKGROUND
  Alzheimer's disease (AD) is diagnosed based upon medical history, neuropsychiatric examination, cerebrospinal fluid analysis, extensive laboratory analyses and cerebral imaging. Diagnosis is time consuming and labour intensive. Parkinson's disease (PD) is mainly diagnosed on clinical grounds.
  
  
  OBJECTIVE
  The primary aim of this study was to differentiate patients suffering from AD, PD and healthy controls by investigating exhaled air with the electronic nose technique. After demonstrating a difference between the three groups the secondary aim was the identification of specific substances responsible for the difference(s) using ion mobility spectroscopy. Thirdly we analysed whether amyloid beta (Aβ) in exhaled breath was causative for the observed differences between patients suffering from AD and healthy controls.
  
  
  METHODS
  We employed novel pulmonary diagnostic tools (electronic nose device/ion-mobility spectrometry) for the identification of patients with neurodegenerative diseases. Specifically, we analysed breath pattern differences in exhaled air of patients with AD, those with PD and healthy controls using the electronic nose device (eNose). Using ion mobility spectrometry (IMS), we identified the compounds responsible for the observed differences in breath patterns. We applied ELISA technique to measure Aβ in exhaled breath condensates.
  
  
  RESULTS
  The eNose was able to differentiate between AD, PD and HC correctly. Using IMS, we identified markers that could be used to differentiate healthy controls from patients with AD and PD with an accuracy of 94%. In addition, patients suffering from PD were identified with sensitivity and specificity of 100%. Altogether, 3 AD patients out of 53 participants were misclassified. Although we found Aβ in exhaled breath condensate from both AD and healthy controls, no significant differences between groups were detected.
  
  
  CONCLUSIONS
  These data may open a new field in the diagnosis of neurodegenerative disease such as Alzheimer's disease and Parkinson's disease. Further research is required to evaluate the significance of these pulmonary findings with respect to the pathophysiology of neurodegenerative disorders.
authors.affiliation: Department of Neurology, RWTH Aachen, 52074 Aachen, Germany.
authors.forename: Jan-Philipp
authors.initials: JP
authors.lastname: Bach
authors.affiliation: Department of Neurology, Philipps-University Marburg, 35043 Marburg, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Gold
authors.affiliation: Department of Neurology, Philipps-University Marburg, 35043 Marburg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Mengel
authors.affiliation: Department of Internal Medicine, Division of Pulmonary Diseases, Philipps-University Marburg, 35043 Marburg, Germany.
authors.forename: Akira
authors.initials: A
authors.lastname: Hattesohl
authors.affiliation: Department of Psychology, Division of Methodology and Statistics of the University of Giessen, 35394 Giessen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Lubbe
authors.affiliation: Department of Internal Medicine, Division of Pulmonary Diseases, Philipps-University Marburg, 35043 Marburg, Germany.
authors.forename: Severin
authors.initials: S
authors.lastname: Schmid
authors.affiliation: Department of Neurology, Philipps-University Marburg, 35043 Marburg, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Tackenberg
authors.affiliation: Department of Neurology, Philipps-University Marburg, 35043 Marburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rieke
authors.affiliation: Faculty of Applied Chemistry, Reutlingen University, 72762 Reutlingen, Germany.
authors.forename: Sasidhar
authors.initials: S
authors.lastname: Maddula
authors.affiliation: Faculty of Applied Chemistry, Reutlingen University, 72762 Reutlingen, Germany.
authors.forename: Jörg Ingo
authors.initials: JI
authors.lastname: Baumbach
authors.affiliation: Department of Internal Medicine, Division of Pulmonary Diseases, Philipps-University Marburg, 35043 Marburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Nell
authors.affiliation: Department of Internal Medicine, Division of Pulmonary Diseases, Philipps-University Marburg, 35043 Marburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Boeselt
authors.affiliation: Clinical Neuroscience Unit, Department of Neurology, University of Bonn, 53105 Bonn, Germany; Department of Psychiatry, University of Bonn, 53105 Bonn, Germany.
authors.forename: Joan
authors.initials: J
authors.lastname: Michelis
authors.affiliation: Department of Psychiatry, University of Bonn, 53105 Bonn, Germany; Department of Psychiatry, University of Münster, 48149 Münster, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Alferink
authors.affiliation: Clinical Neuroscience Unit, Department of Neurology, University of Bonn, 53105 Bonn, Germany; German Centre for Neurodegenerative Disease (DZNE), 53105 Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Heneka
authors.affiliation: Department of Neurology, Philipps-University Marburg, 35043 Marburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Oertel
authors.affiliation: Department of Psychiatry, University of Bonn, 53105 Bonn, Germany; German Centre for Neurodegenerative Disease (DZNE), 53105 Bonn, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Jessen
authors.affiliation: Department of Internal Medicine, University of Hannover, 30625 Hannover, Germany.
authors.forename: Sabina
authors.initials: S
authors.lastname: Janciauskiene
authors.affiliation: Department of Internal Medicine, Division of Pulmonary Diseases, Philipps-University Marburg, 35043 Marburg, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Vogelmeier
authors.affiliation: Department of Neurology, Philipps-University Marburg, 35043 Marburg, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Dodel
authors.affiliation: Department of Internal Medicine, Division of Pulmonary Diseases, Philipps-University Marburg, 35043 Marburg, Germany.
authors.forename: Andreas Rembert
authors.initials: AR
authors.lastname: Koczulla
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000032:analysis; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D001944:Breath Tests / Q000379:methods; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008168:Lung / Q000737:chemistry; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis*; D010446:Peptide Fragments / Q000032:analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)