Identification of a new plasma biomarker of Alzheimer's disease using metabolomics technology

We performed unbiased analysis of steroid-related compounds to identify novel Alzheimer's disease (AD) plasma biomarkers using liquid chromatography-atmospheric pressure chemical ionization-mass spectroscopy. The analysis revealed that desmosterol was found to be decreased in AD plasma versus c...

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Bibliographic Details
Published in:Journal of lipid research 2012-03, Vol.53 (3), p.567-576
Main Authors: Sato, Yoshiaki, Suzuki, Ikumi, Nakamura, Tatsuji, Bernier, Francois, Aoshima, Ken, Oda, Yoshiya
Format: Article
Language:English
Subjects:
Aged
Alzheimer Disease - blood
Biomarkers - blood
Case-Control Studies
cholesterol
Cholesterol - blood
Chromatography, Liquid
desmosterol
Desmosterol - blood
Female
Humans
lipidomics
Male
Mass Spectrometry
Metabolomics - methods
mild cognitive impairment patients
Patient-Oriented and Epidemiological Research
Sex Factors
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Summary:We performed unbiased analysis of steroid-related compounds to identify novel Alzheimer's disease (AD) plasma biomarkers using liquid chromatography-atmospheric pressure chemical ionization-mass spectroscopy. The analysis revealed that desmosterol was found to be decreased in AD plasma versus controls. To precisely quantify variations in desmosterol, we established an analytical method to measure desmosterol and cholesterol. Using this LC-based method, we discovered that desmosterol and the desmosterol/cholesterol ratio are significantly decreased in AD. Finally, the validation of this assay using 109 clinical samples confirmed the decrease of desmosterol in AD as well as a change in the desmosterol/cholesterol ratio in AD. Interestingly, we could also observe a difference between mild cognitive impairment and control. In addition, the decrease of desmosterol was somewhat more significant in females. Receiver operating characteristic (ROC) analysis between controls and AD, using plasma desmosterol shows a score of 0.80, indicating a good discrimination power for this marker in the two reference populations and confirms the potential usefulness of measuring plasma desmosterol levels for diagnosing AD. Further analysis showed a significant correlation of plasma desmosterol with Mini-Mental State Examination scores. Although larger sample populations will be needed to confirm this diagnostic marker sensitivity, our studies demonstrate a sensitive and accurate method of detecting plasma desmosterol concentration and suggest that plasma desmosterol could become a powerful new specific biomarker for early and easy AD diagnosis.
ISSN:0022-2275
1539-7262
DOI:10.1194/jlr.M022376