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Analysis of chiral amino acids in cerebrospinal fluid samples linked to different stages of Alzheimer disease.
Electrophoresis. 2011 Oct; 32(19):2757-64.E

Abstract

Chiral micellar electrokinetic chromatography with laser-induced fluorescence detection (chiral-MEKC-LIF) was used to investigate D- and L-amino acid contents in cerebrospinal fluid (CSF) samples related to different Alzheimer disease (AD) stages. CSF samples were taken from (i) control subjects (S1 pool), (ii) subjects showing a mild cognitive impairment who remained stable (S2 pool), (iii) subjects showing an mild cognitive impairment that progressed to AD (S3 pool) and (iv) subjects diagnosed with AD (S4 pool). The optimized procedure only needed 10 μL of CSF and it included sample cleaning, derivatization with FITC and chiral-MEKC-LIF separation. Eighteen standard amino acids were baseline separated with efficiencies up to 703,000 plates/m, high sensitivity (LODs in the nM range) and good resolution (values ranging from 2.6 to 9.5). Using this method, L-Arg, L-Leu, L-Gln, γ-aminobutyric acid, L-Ser, D-Ser, L-Ala, Gly, L-Lys, L-Glu and L-Asp were detected in all the CSF samples. S3 and S4 samples (i.e. AD subjects) showed significant lower amounts of L-Arg L-Lys, L-Glu and L-Asp compared to the non-AD S1 and S2 samples, showing in the S4 group the lowest amounts of L-Arg L-Lys, L-Glu and L-Asp. Moreover, γ-aminobutyric acid was significantly higher in AD subjects with the highest amount also found for S4. No significant differences were observed for the rest of amino acids including D-Ser. Based on the obtained chiral-MEKC-LIF data, it was possible to correctly classify all the samples into the four groups. These results demonstrate that the use of enantioselective procedures as the one developed in this work can provide some new light on the investigations of AD, including the discovery of new biomarkers related to different stages of AD.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Samakashvili S
Department of Physical and Analytical Chemistry, School of Exact and Natural Sciences, Tbilisi State University, Tbilisi, Georgia.
Ibáñez C
No affiliation info available
Simó C
No affiliation info available
Gil-Bea FJ
No affiliation info available
Winblad B
No affiliation info available
Cedazo-Mínguez A
No affiliation info available
Cifuentes A
No affiliation info available

MeSH

Alzheimer DiseaseAmino AcidsAnalysis of VarianceBiomarkersCase-Control StudiesChromatography, Micellar Electrokinetic CapillaryDisease ProgressionHumansReproducibility of ResultsSensitivity and SpecificityStereoisomerism

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21983823

Citation

Samakashvili, Shorena, et al. "Analysis of Chiral Amino Acids in Cerebrospinal Fluid Samples Linked to Different Stages of Alzheimer Disease." Electrophoresis, vol. 32, no. 19, 2011, pp. 2757-64.
Samakashvili S, Ibáñez C, Simó C, et al. Analysis of chiral amino acids in cerebrospinal fluid samples linked to different stages of Alzheimer disease. Electrophoresis. 2011;32(19):2757-64.
Samakashvili, S., Ibáñez, C., Simó, C., Gil-Bea, F. J., Winblad, B., Cedazo-Mínguez, A., & Cifuentes, A. (2011). Analysis of chiral amino acids in cerebrospinal fluid samples linked to different stages of Alzheimer disease. Electrophoresis, 32(19), 2757-64. https://doi.org/10.1002/elps.201100139
Samakashvili S, et al. Analysis of Chiral Amino Acids in Cerebrospinal Fluid Samples Linked to Different Stages of Alzheimer Disease. Electrophoresis. 2011;32(19):2757-64. PubMed PMID: 21983823.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of chiral amino acids in cerebrospinal fluid samples linked to different stages of Alzheimer disease. AU - Samakashvili,Shorena, AU - Ibáñez,Clara, AU - Simó,Carolina, AU - Gil-Bea,Francisco J, AU - Winblad,Bengt, AU - Cedazo-Mínguez,Angel, AU - Cifuentes,Alejandro, Y1 - 2011/08/29/ PY - 2011/03/01/received PY - 2011/04/13/revised PY - 2011/04/15/accepted PY - 2011/10/11/entrez PY - 2011/10/11/pubmed PY - 2011/12/30/medline SP - 2757 EP - 64 JF - Electrophoresis JO - Electrophoresis VL - 32 IS - 19 N2 - Chiral micellar electrokinetic chromatography with laser-induced fluorescence detection (chiral-MEKC-LIF) was used to investigate D- and L-amino acid contents in cerebrospinal fluid (CSF) samples related to different Alzheimer disease (AD) stages. CSF samples were taken from (i) control subjects (S1 pool), (ii) subjects showing a mild cognitive impairment who remained stable (S2 pool), (iii) subjects showing an mild cognitive impairment that progressed to AD (S3 pool) and (iv) subjects diagnosed with AD (S4 pool). The optimized procedure only needed 10 μL of CSF and it included sample cleaning, derivatization with FITC and chiral-MEKC-LIF separation. Eighteen standard amino acids were baseline separated with efficiencies up to 703,000 plates/m, high sensitivity (LODs in the nM range) and good resolution (values ranging from 2.6 to 9.5). Using this method, L-Arg, L-Leu, L-Gln, γ-aminobutyric acid, L-Ser, D-Ser, L-Ala, Gly, L-Lys, L-Glu and L-Asp were detected in all the CSF samples. S3 and S4 samples (i.e. AD subjects) showed significant lower amounts of L-Arg L-Lys, L-Glu and L-Asp compared to the non-AD S1 and S2 samples, showing in the S4 group the lowest amounts of L-Arg L-Lys, L-Glu and L-Asp. Moreover, γ-aminobutyric acid was significantly higher in AD subjects with the highest amount also found for S4. No significant differences were observed for the rest of amino acids including D-Ser. Based on the obtained chiral-MEKC-LIF data, it was possible to correctly classify all the samples into the four groups. These results demonstrate that the use of enantioselective procedures as the one developed in this work can provide some new light on the investigations of AD, including the discovery of new biomarkers related to different stages of AD. SN - 1522-2683 UR - https://www.unboundmedicine.com/medline/citation/21983823/Analysis_of_chiral_amino_acids_in_cerebrospinal_fluid_samples_linked_to_different_stages_of_Alzheimer_disease_ L2 - https://doi.org/10.1002/elps.201100139 DB - PRIME DP - Unbound Medicine ER -