Hsien-Yuan Lane1,2,3, Chieh-Hsin Lin2,4,5. 1. Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan. 2. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan. 3. Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung, Taiwan. 4. Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan. 5. School of Medicine, Chang Gung University, Taoyuan, Taiwan.
Abstract
BACKGROUND: Reliable blood biomarkers for Alzheimer's disease (AD) have been lacking. The D-amino acids oxidase (DAAO) modulator (named pLG72) modulates glutamate NMDAR activity. The cystine/glutamate antiporter contains a SLC7A11 subunit, which mediates glutamate release. This study aimed to determine the accuracy of pLG72 protein and SLC7A11 mRNA in diagnosing AD. METHODS: This study enrolled 130 healthy controls and 109 unmatched AD patients; among them, 40 controls and 70 patients were selected to match by age. We measured their pLG72 protein in plasma and SLC7A11 mRNA in white blood cells. RESULTS: AD patients had markedly higher pLG72 levels and SLC7A11 mRNA ΔCT values than healthy controls (in both unmatched and matched cohorts; all four p values <0.001). The receiver operating characteristics analysis in the unmatched cohorts demonstrated that the pLG72 level had a high specificity (0.900) at the optimal cutoff value of 2.3285, the ΔCT of SLC7A11 mRNA displayed an excellent sensitivity (0.954) at the cutoff of 12.185, and the combined value of pLG72 and SLC7A11 ΔCT determined a favorable AUC (0.882) at the cutoff of 21.721. The AUC of the combined value surpassed that of either biomarker. The specificity, sensitivity, and AUC of the matched cohort were similar to those of the unmatched cohort. CONCLUSIONS: The findings suggest that pLG72 protein and SLC7A11 mRNA can distinguish AD patients from healthy controls with excellent specificity and sensitivity, respectively. The combination of pLG72 and SLC7A11 yields better AUC than either, suggesting the superiority of simultaneously measuring both biomarkers in identifying AD patients.
BACKGROUND: Reliable blood biomarkers for Alzheimer's disease (AD) have been lacking. The D-amino acids oxidase (DAAO) modulator (named pLG72) modulates glutamate NMDAR activity. The cystine/glutamate antiporter contains a SLC7A11 subunit, which mediates glutamate release. This study aimed to determine the accuracy of pLG72 protein and SLC7A11 mRNA in diagnosing AD. METHODS: This study enrolled 130 healthy controls and 109 unmatched AD patients; among them, 40 controls and 70 patients were selected to match by age. We measured their pLG72 protein in plasma and SLC7A11 mRNA in white blood cells. RESULTS: AD patients had markedly higher pLG72 levels and SLC7A11 mRNA ΔCT values than healthy controls (in both unmatched and matched cohorts; all four p values <0.001). The receiver operating characteristics analysis in the unmatched cohorts demonstrated that the pLG72 level had a high specificity (0.900) at the optimal cutoff value of 2.3285, the ΔCT of SLC7A11 mRNA displayed an excellent sensitivity (0.954) at the cutoff of 12.185, and the combined value of pLG72 and SLC7A11 ΔCT determined a favorable AUC (0.882) at the cutoff of 21.721. The AUC of the combined value surpassed that of either biomarker. The specificity, sensitivity, and AUC of the matched cohort were similar to those of the unmatched cohort. CONCLUSIONS: The findings suggest that pLG72 protein and SLC7A11 mRNA can distinguish AD patients from healthy controls with excellent specificity and sensitivity, respectively. The combination of pLG72 and SLC7A11 yields better AUC than either, suggesting the superiority of simultaneously measuring both biomarkers in identifying AD patients.