Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values

Abstract

Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and restricted and repetitive behaviors. Neuroinflammation and abnormal lipid mediators have been identified in multiple investigations as an acknowledged etiological mechanism of ASD that can be targeted for therapeutic intervention. Methods In this study, multiple regression and combined receiver operating characteristic (ROC) curve analyses were used to determine the relationship between the neuroinflammatory marker α-synuclein and lipid mediator markers related to inflammation induction, such as cyclooxygenase-2 and prostaglandin-EP2 receptors, in the etiology of ASD. Additionally, the study aimed to determine the linear combination that maximizes the partial area under ROC curves for a set of markers. Forty children with ASD and 40 age- and sex-matched controls were enrolled in the study. Using ELISA, the levels of α-synuclein, cyclo-oxygenase-2, and prostaglandin-EP2 receptors were measured in the plasma of both groups. Statistical analyses using ROC curves and multiple and logistic regression models were performed. Results A remarkable increase in the area under the curve was observed using combined ROC curve analyses. Moreover, higher specificity and sensitivity of the combined markers were reported. Conclusions The present study indicates that measurement of the predictive value of selected biomarkers related to neuroinflammation and lipid metabolism in children with ASD using a ROC curve analysis should lead to a better understanding of the etiological mechanism of ASD and its link with metabolism. This information may facilitate early diagnosis and intervention.

Lipid-Based Molecules on Signaling Pathways in Autism Spectrum Disorder

“…Significantly higher levels of both COX-2 and PGE2 have been reported in the plasma samples of autistic patients. Increased plasma PGE2 levels were concomitant with significantly lower levels of α-synuclein [ 23 ], which plays a critical role in synaptic functions, including synaptic pool preservation, vesicular stabilization, and synaptic plasticity [ 23 ]. The combination of α-Syn, COX-2, and PGE2/its EP2 receptor may be a predictive diagnostic biomarker of ASD in relation to mitochondrial dysfunction and glutamate excitotoxicity as etiological mechanisms of ASD, indicating that the above-described diagnostic markers might contribute to early intervention [ 23 ].…”

“…The two cannabinoid receptors, CB1 and CB2, are derivatives of PUFAω-6 AA and ω-3 fatty acids Wu [ 23 ]. The ECS plays a role in modulating behavioral traits [ 29 ].…”

Assessment of a combination of plasma anti-histone autoantibodies and PLA2/PE ratio as potential biomarkers to clinically predict autism spectrum disorders

“…Logistic regression was performed between the twenty four variables with all possible permutations, and two models of combined ROC that have significant increase in the AUC of one or more variable were considered Supplementary Table S1 . First model was published as combined Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of ASD 38 . The second model is that presented in the current study showing combination between anti-histone autoantibodies with PLA2/PE relative ratio as a perfect biomarker of pro-inflammation and membrane phospholipid alteration in ASD.…”

In vivo anticancer study of sodium 2‐[(4‐oxidobenzylidene)amino]‐6H‐1,3,4‐thiadiazine‐5‐olate against Ehrlich ascites carcinoma via targeting PI3K/mTOR pathway

“…Using the same computer tool, the receiver‐operating characteristics' (ROC) curve was calculated as a helpful metric for assessing the utility of biomarkers. To quantify the association between the investigated parameters, the Pearson's correlation test was utilized to determine the relationship among the variables (El‐Ansary et al., 2021).…”