Background: D-amino acids are closely related to the development and progression of Alzheimer's disease (AD) and are expected as the novel biomarkers for AD diagnosis.
Objective: The aim was to investigate the potential clinical value of D-amino acids for Alzheimer's disease.
Methods: A simple and sensitive HPLC/MS-MS method was developed for the simultaneous determination of D-alanine, D-glutamine, D-proline and D-serine in rat urine. The samples were firstly pretreated by methanol, then derivatized by 7-chloro-4-nitrobenzoxadiazole with Fudosteine as internal standard, enantioseparated on Sumichiral OA-2500S column, using a mobile phase composed of acetonitrile- methanol (50:50, v/v) containing 0.5% formic acid, and detected with 4000 Qtrap MS/MS in electrospray-ionization source by negative ion mode.
Results: The established method was successfully applied to determine the D-amino acid levels in rat urine from 20 Alzheimer's disease rats and 20 age-matched normal controls. The mean levels of Damino acids in the urine of Alzheimer's disease rats were all significantly lower than those in normal controls. Based on the contents of D-amino acids, the distinction model between Alzheimer's disease rats and normal controls was established by the Bayesian discriminant analysis.
Conclusion: The relationship between Alzheimer's disease and D-amino acids revealed that D-amino acids would be potential biomarkers for Alzheimer’s disease.
[http://dx.doi.org/10.1016/j.brainresbull.2014.11.003] [PMID: 25446738]
[http://dx.doi.org/10.1016/S1474-4422(10)70223-4] [PMID: 20934914]
[http://dx.doi.org/10.1016/j.jalz.2011.03.003] [PMID: 21514248]
[http://dx.doi.org/10.1016/j.jalz.2011.03.005] [PMID: 21514250]
[http://dx.doi.org/10.1016/S1474-4422(07)70178-3] [PMID: 17616482]
[http://dx.doi.org/10.1016/S1474-4422(09)70139-5] [PMID: 19523877]
[http://dx.doi.org/10.1373/clinchem.2009.130518] [PMID: 19833838]
[http://dx.doi.org/10.1016/j.chroma.2013.11.026] [PMID: 24315356]
[http://dx.doi.org/10.1016/j.jchromb.2017.05.011] [PMID: 28531844]
[http://dx.doi.org/10.1038/tp.2015.52] [PMID: 25942042]
[http://dx.doi.org/10.1016/j.neuron.2014.09.039] [PMID: 25447741]
[http://dx.doi.org/10.1007/s00216-015-9086-3] [PMID: 26497841]
[http://dx.doi.org/10.1002/1522-2683(200108)22:13<2769:AID-ELPS2769>3.0.CO;2-H] [PMID: 11545406]
[http://dx.doi.org/10.1210/en.2005-0692] [PMID: 16254026]
[http://dx.doi.org/10.1007/s00401-011-0873-4] [PMID: 21927944]
[http://dx.doi.org/10.1073/pnas.0408483102] [PMID: 15800046]
[http://dx.doi.org/10.1111/j.1474-9726.2006.00216.x] [PMID: 16842499]
[http://dx.doi.org/10.1111/j.1742-4658.2008.06515.x] [PMID: 18564180]
[http://dx.doi.org/10.3233/JAD-2009-1194] [PMID: 20009237]
[http://dx.doi.org/10.1016/j.jchromb.2011.06.028] [PMID: 21757409]