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Rabia Latif,1 Nazish Rafique,1 Lubna Al Asoom,1 Ahmed A Alsunni,1 Ayad Mohammed Salem,1 Dinah Abdulhadi AlNoaimi,2 Wasan Mohammed AlHarbi,2 Ahad Yasir Shaikh,2 Shoug Abdullah AlRaddadi,2 Leena Abdulrahman AlMuhaish,2 Dana Almohazey,3 Sayed Abdulazeez,4 J Francis Borgio4 1Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 3Department of Stem Cell Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 4Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaCorrespondence: Rabia LatifDepartment of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam, 31441, Saudi ArabiaTel +966 596212648Fax +966 38578048Email rlhussain@iau.edu.saBackground: A reliable, migraine-specific biomarker has not been identified so far. Calcitonin Gene-Related Peptide (CGRP) and Apolipoprotein E (ApoE) might serve as migraine biomarkers due to their roles in migraine pathophysiology. However, their diagnostic usefulness has not been explored yet. Present study explored the diagnostic accuracy of CGRP and ApoE in migraine.Methods: A cross-sectional, case–control study was conducted from November 2019 to April 2020 at Physiology department of our university. Fourteen female migraine patients, 18– 25 years old, with confirmed “Migraine” diagnosis by a neurologist, were recruited. Control group consisted of 14 age-matched healthy females with no personal/family history of migraine. Blood was drawn once from control subjects and twice from migraine patients (ictal and interictal phase). Serum CGRP and ApoE levels were assessed by ELISA. Statistical analysis involved paired t-test, one-way ANOVA, Receiver operating characteristic (ROC) curves and cross-tabs.Results: ApoE (mg/dl) was higher significantly in interictal (1.90± 0.50) and ictal (1.97± 0.65) phases of migraine compared to control (1.07± 0.26) (p ≤ 0.001). ROC curves for ApoE were significant in migraine ictal vs control (AUC= 0.91, AUC 95% CI: 0.78– 1.0) and migraine interictal vs control (AUC=0.92, AUC 95% CI: 0.8– 1.0) subjects. ROC curve for CGRP (pg/mL) was significant in migraine ictal vs control subjects only (AUC=0.79, AUC 95% CI: 0.6– 0.97).Conclusion: Serum ApoE has “excellent” accuracy to diagnose migraine patients whether in ictal or interictal phase, from healthy subjects. ApoE levels of patients in these two phases of migraine are raised significantly than healthy subjects. CGRP has “fair” diagnostic accuracy to discriminate between migraine ictal phase and healthy subjects. Its levels do not differ significantly among migraine ictal, interictal phase and healthy controls.Keywords: apolipoprotein E, calcitonin gene-related peptide, migraine, receiver operating curve, biomarkers