{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T01:48:24Z","timestamp":1781574504435,"version":"3.54.5"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Alzheimer\u2019s 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-\u03b242\/amyloid-\u03b240 (A\u03b242\/A\u03b240) 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 A\u03b242\/A\u03b240 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\u20130.97). 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.<\/jats:p>","DOI":"10.3390\/biom16030356","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T16:57:13Z","timestamp":1772125033000},"page":"356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Plasma-Derived hsa_circ_003077 for Non-Invasive Diagnosis of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"16","author":[{"given":"Hamit","family":"\u00c7elik","sequence":"first","affiliation":[{"name":"Department of Neurology, Private Buhara Hospital, 25240 Erzurum, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O\u011fuz","family":"\u00c7elik","sequence":"additional","affiliation":[{"name":"Savur Prof. Dr. Aziz Sancar District State Hospital, 47860 Mardin, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5640-3363","authenticated-orcid":false,"given":"\u015eeyma","family":"Ayd\u0131n","sequence":"additional","affiliation":[{"name":"Department of Genetics, Faculty of Veterinary Medicine, Atat\u00fcrk University, 25240 Erzurum, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sefa","family":"K\u00fc\u00e7\u00fckler","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Veterinary Medicine, Atat\u00fcrk University, 25240 Erzurum, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selim","family":"\u00c7omakl\u0131","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine, Atat\u00fcrk University, 25240 Erzurum, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramazan","family":"Akay","sequence":"additional","affiliation":[{"name":"Department of Neurology, Eskisehir City Hospital, 26080 Eski\u015fehir, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6252-3216","authenticated-orcid":false,"given":"Sinan","family":"G\u00f6n\u00fcll\u00fc","sequence":"additional","affiliation":[{"name":"Department of Neurology, Bursa City Hospital, 16250 Bursa, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa Onur","family":"Y\u0131ld\u0131z","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Samsun University, 55060 Samsun, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00fclent","family":"Al\u0131m","sequence":"additional","affiliation":[{"name":"Department of Neurology, Private Buhara Hospital, 25240 Erzurum, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7539-0523","authenticated-orcid":false,"given":"Sel\u00e7uk","family":"\u00d6zdemir","sequence":"additional","affiliation":[{"name":"Department of Genetics, Faculty of Veterinary Medicine, Atat\u00fcrk University, 25240 Erzurum, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5395","DOI":"10.1007\/s12035-024-04617-3","article-title":"Integration of Single-Cell and Spatial Transcriptomic Data Reveals Spatial Architecture and Potential Biomarkers in Alzheimer\u2019s Disease","volume":"62","author":"Fan","year":"2025","journal-title":"Mol. 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