title: Metabolite profiling of Alzheimer's disease cerebrospinal fluid.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of cognitive functions. Today the diagnosis of AD relies on clinical evaluations and is only late in the disease. Biomarkers for early detection of the underlying neuropathological changes are still lacking and the biochemical pathways leading to the disease are still not completely understood. The aim of this study was to identify the metabolic changes resulting from the disease phenotype by a thorough and systematic metabolite profiling approach. For this purpose CSF samples from 79 AD patients and 51 healthy controls were analyzed by gas and liquid chromatography-tandem mass spectrometry (GC-MS and LC-MS/MS) in conjunction with univariate and multivariate statistical analyses. In total 343 different analytes have been identified. Significant changes in the metabolite profile of AD patients compared to healthy controls have been identified. Increased cortisol levels seemed to be related to the progression of AD and have been detected in more severe forms of AD. Increased cysteine associated with decreased uridine was the best paired combination to identify light AD (MMSE>22) with specificity and sensitivity above 75%. In this group of patients, sensitivity and specificity above 80% were obtained for several combinations of three to five metabolites, including cortisol and various amino acids, in addition to cysteine and uridine.
authors.affiliation: F. Hoffmann-La Roche, Pharmaceuticals Division, Basel, Switzerland. christian.czech@roche.com
authors.forename: Christian
authors.initials: C
authors.lastname: Czech
authors.forename: Peter
authors.initials: P
authors.lastname: Berndt
authors.forename: Kristina
authors.initials: K
authors.lastname: Busch
authors.forename: Oliver
authors.initials: O
authors.lastname: Schmitz
authors.forename: Jan
authors.initials: J
authors.lastname: Wiemer
authors.forename: Veronique
authors.initials: V
authors.lastname: Most
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kastler
authors.forename: Hans
authors.initials: H
authors.lastname: Senn
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000378:metabolism; D016022:Case-Control Studies; D003545:Cysteine / Q000134:cerebrospinal fluid; D018450:Disease Progression; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006854:Hydrocortisone / Q000134:cerebrospinal fluid; D055442:Metabolome; D012680:Sensitivity and Specificity; D014529:Uridine / Q000134:cerebrospinal fluid
chemical_list: D003545:Cysteine; D014529:Uridine; D006854:Hydrocortisone