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Metabolites. 2014 Feb 19;4(1):115-28. doi: 10.3390/metabo4010115.

1H NMR Analysis of Cerebrospinal Fluid from Alzheimer's Disease Patients: An Example of a Possible Misinterpretation Due to Non-Adjustment of pH.

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  • 1Université de Toulouse, UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Groupe de RMN Biomédicale, 118 route de Narbonne, 31062 Toulouse cedex 9, France. cruz@chimie.ups-tlse.fr.
  • 2Université de Toulouse, UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Groupe de RMN Biomédicale, 118 route de Narbonne, 31062 Toulouse cedex 9, France. balayssac@chimie.ups-tlse.fr.
  • 3Université de Toulouse, UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Groupe de RMN Biomédicale, 118 route de Narbonne, 31062 Toulouse cedex 9, France. gilard@chimie.ups-tlse.fr.
  • 4Université de Toulouse, UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Groupe de RMN Biomédicale, 118 route de Narbonne, 31062 Toulouse cedex 9, France. rmartino@chimie.ups-tlse.fr.
  • 5CHU Purpan, Laboratoire de Biologie cellulaire et Cytologie, Institut Fédératif de Biologie, 330, avenue de Grande-Bretagne, 31059 Toulouse cedex 9, France. vincent.c@chu-toulouse.fr.
  • 6Université de Toulouse, UPS, CHU Purpan, Imagerie cérébrale et handicaps neurologiques, UMR 825, 31059 Toulouse cedex 9, France. jeremie.pariente@inserm.fr.
  • 7Université de Toulouse, UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Groupe de RMN Biomédicale, 118 route de Narbonne, 31062 Toulouse cedex 9, France. martino@chimie.ups-tlse.fr.

Abstract

Two publications from the same research group reporting on the detection of new possible biomarkers for the early diagnosis of Alzheimer's disease (AD), based on the analysis of cerebrospinal fluid samples (CSF) with 1H Nuclear Magnetic Resonance (NMR), are at the origin of the present study. The authors observed significant differences in 1H NMR spectra of CSF from AD patients and healthy controls and, thus, proposed some NMR signals (without attribution) as possible biomarkers. However, this work was carried out in non-standardized pH conditions. Our study aims at warning about a possible misinterpretation that can arise from 1H NMR analyses of CSF samples if pH adjustment is not done before NMR analysis. Indeed, CSF pH increases rapidly after removal and is subject to changes over conservation time. We first identify the NMR signals described by the authors as biomarkers. We then focus on the chemical shift variations of their NMR signals as a function of pH in both standard solutions and CSF samples. Finally, a principal component analysis of 1H NMR data demonstrates that the same CSF samples recorded at pH 8.1 and 10.0 are statistically differentiated.

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