Evaluation of Plasma-Derived hsa_circ_003077 for Non-Invasive Diagnosis of Alzheimer’s Disease

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Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting the central nervous system and is the most common form of dementia in the elderly. Current diagnostic methods are limited in the early and definitive diagnosis of the disease, necessitating the need for new and more reliable biomarkers. Circular RNAs (circRNAs) are non-coding, single-stranded, and highly stable RNA molecules commonly found in the eukaryotic transcriptome. Recent studies have shown that changes in the expression levels of circRNAs may play a role in AD pathogenesis. Furthermore, these molecules are considered as potential non-invasive biomarkers for early diagnosis of AD. In this study, we comprehensively assessed plasma levels of classical neurodegenerative biomarkers [amyloid-β42/amyloid-β40 (Aβ42/Aβ40) ratio, total Tau (tTau), and phosphorylated Tau (pTau)], as well as glial and inflammatory mediators, TAM receptor family members (Tyro3 and AXL), and the newly identified circular RNA molecule hsa_circ_003077. The findings revealed that the expression levels of TAM receptors were significantly increased, the Aβ42/Aβ40 ratio decreased, and both total Tau and phosphorylated Tau levels were significantly increased in AD patients. In the receiver operating characteristic (ROC) curve analysis performed to determine the diagnostic potential of hsa_circ_003077, the area under the curve (AUC) was 0.90 (95% CI: 0.82–0.97). This high AUC value suggests that hsa_circ_003077 may be a strong and novel biomarker candidate for the non-invasive diagnosis of AD. The data obtained confirmed the diagnostic efficacy of classical AD biomarkers and revealed that hsa_circ_003077 is a promising biomarker for early and accurate detection of the disease. However, in order to assess the transferability of these findings to clinical practice, confirmatory studies with larger sample groups are needed to ensure reproducibility of the results.

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