Metabolites 2014, 4(1), 115-128; doi:10.3390/metabo4010115
Article

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

1email, 1email, 1email, 1email, 2email, 3email and 1,* email
Received: 2 December 2013; in revised form: 10 January 2014 / Accepted: 7 February 2014 / Published: 19 February 2014
(This article belongs to the Special Issue Sample Preparation for Metabolite Analysis)
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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.
Keywords: 1H NMR; cerebrospinal fluid; Alzheimer’s disease; metabolites; chemical shift pH dependence
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Cruz, T.; Balayssac, S.; Gilard, V.; Martino, R.; Vincent, C.; Pariente, J.; Malet-Martino, M. 1H NMR Analysis of Cerebrospinal Fluid from Alzheimer’s Disease Patients: An Example of a Possible Misinterpretation Due to Non-Adjustment of pH. Metabolites 2014, 4, 115-128.

AMA Style

Cruz T, Balayssac S, Gilard V, Martino R, Vincent C, Pariente J, Malet-Martino M. 1H NMR Analysis of Cerebrospinal Fluid from Alzheimer’s Disease Patients: An Example of a Possible Misinterpretation Due to Non-Adjustment of pH. Metabolites. 2014; 4(1):115-128.

Chicago/Turabian Style

Cruz, Thomas; Balayssac, Stéphane; Gilard, Véronique; Martino, Robert; Vincent, Christian; Pariente, Jérémie; Malet-Martino, Myriam. 2014. "1H NMR Analysis of Cerebrospinal Fluid from Alzheimer’s Disease Patients: An Example of a Possible Misinterpretation Due to Non-Adjustment of pH." Metabolites 4, no. 1: 115-128.


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