{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:00:44Z","timestamp":1789988444085,"version":"4.0.1"},"reference-count":24,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Impaired autophagy has been implicated in neurodegeneration, but circulating autophagy-related proteins have shown inconsistent associations with cognitive impairment. We compared serum autophagy-related protein 5 (ATG5) among older adults with normal cognition, mild cognitive impairment (MCI), and clinically diagnosed Alzheimer\u2019s disease (AD), and examined its relationship with global cognitive performance. Materials and Methods: This single-centre cross-sectional study enrolled 164 older adults (55 with normal cognition, 55 with MCI, and 54 with clinically diagnosed AD). Cognitive status was determined through integrated clinical assessment rather than a single test cut-off. An enzyme-linked immunosorbent assay was employed to quantify serum ATG5, yielding quantifiable values for 156 participants, right-censored observations above the highest calibrator for six, and unmeasurable results for two. Since the two 96-well plates, drawn from one ELISA kit lot and processed on the same day, exhibited a substantial discrepancy in measurement scale across runs, they were analysed as distinct strata, with the principal group contrast estimated via a right-censored Tobit regression of log-transformed ATG5 within each plate, controlling for cognitive group, age and sex; a pooled plate-adjusted model also provided support. Supportive analyses used within-plate z-standardised ATG5. Associations with clinical variables were assessed using age- and sex-adjusted partial Spearman correlations with false discovery rate correction. Results: Across both analytical strata (plate 1 omnibus p = 0.293; plate 2 p = 0.264) and within the supportive pooled model (p = 0.143; AD vs. normal geometric mean ratio 0.89, 95% CI 0.73\u20131.09), serum ATG5 concentrations did not differ significantly between cognitive groups. Concentrations on plate 2 were 47% lower (GMR 0.53, 95% CI 0.45\u20130.62), a gap exceeding the inter-assay imprecision declared by the manufacturer and unexplained by the calibrator values from plate 2; since relative dispersion matched across both plates (likelihood ratio p = 0.730), the pattern suggests a multiplicative scale shift of unknown origin. Serum ATG5 levels were weakly associated with global cognitive performance assessed via the S-MMSE (partial \u03c1 = 0.283, p &lt; 0.001, FDR p = 0.010), an association that persisted after adjusting for education, albumin and folate and retained a similar magnitude within a linear model (\u03b2 = 0.044, p = 0.014). Incorporating ATG5 into a model that included age, sex and education failed to enhance discrimination (\u0394AUC +0.012 and +0.000). Conclusions: Serum ATG5 did not discriminate normal cognition, MCI, and clinically diagnosed AD. A weak rank-based association with S-MMSE was observed, but the effect was small. These findings do not support serum ATG5 as a diagnostic discriminator for clinically defined cognitive status.<\/jats:p>","DOI":"10.3390\/medicina62091722","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:12:25Z","timestamp":1788783145000},"page":"1722","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum Autophagy-Related Protein 5 and Clinically Defined Cognitive Status in Older Adults: A Plate-Stratified Cross-Sectional Study Across: Normal Cognition, Mild Cognitive Impairment, and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9193-5327","authenticated-orcid":false,"given":"K\u00fcbra","family":"Erdo\u011fan","sequence":"first","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine, Ankara Bilkent City Hospital, 06200 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cemile","family":"Bi\u00e7er","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University, 06760 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1939-4738","authenticated-orcid":false,"given":"R\u0131dvan","family":"Erten","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine, Faculty of Medicine, Kocaeli University, 41380 Kocaeli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00fcbra","family":"Kaya","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Faculty of Medicine, Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University, 06760 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serap","family":"Boz","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine, Ankara Bilkent City Hospital, 06200 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3992-7438","authenticated-orcid":false,"given":"Hatice","family":"Turgut \u015eahin","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine, Ankara Bilkent City Hospital, 06200 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0518-4263","authenticated-orcid":false,"given":"Cemile","family":"Peker","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine, Ankara Bilkent City Hospital, 06200 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arzu Nevin","family":"Da\u011fdemir","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine, Ankara Bilkent City Hospital, 06200 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0244-4866","authenticated-orcid":false,"given":"B\u00fc\u015frag\u00fcl","family":"Y\u0131lmaz","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine, Ankara Bilkent City Hospital, 06200 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asl\u0131han","family":"Y\u0131ld\u0131r\u0131m","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine, Ankara Bilkent City Hospital, 06200 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Tuna Do\u011frul","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine, Ankara Bilkent City Hospital, 06200 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hande","family":"Selvi \u00d6ztorun","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine, Faculty of Medicine, Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University, 06760 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4766-3982","authenticated-orcid":false,"given":"G\u00fcne\u015f","family":"Eken","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine, Faculty of Medicine, Health Science University, 06230 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0384-4957","authenticated-orcid":false,"given":"Kamile","family":"S\u0131lay","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine, Faculty of Medicine, Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University, 06760 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref_1","unstructured":"GBD 2019 Dementia Forecasting Collaborators (2022). 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