{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:29:56Z","timestamp":1779910196360,"version":"3.53.1"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Glutathione S-transferase alpha (GST\u03b1) is an important antioxidant enzyme closely associated with the onset and progression of neurodegenerative diseases. The alterations in GST\u03b1 protein levels associated with Alzheimer\u2019s disease and their impact on cognitive abilities remain unclear. Thus, investigating the fluctuations of GST\u03b1 protein levels in mild cognitive impairment (MCI) and Alzheimer\u2019s disease (AD) is essential.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DATA were enrolled from the Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI) database, and we studied healthy individuals (as controls, a total of 54), patients with mild cognitive impairment (345), and patients with Alzheimer\u2019s disease (96) A one-year follow-up was conducted to collect data on the dynamic changes of GST\u03b1 protein levels in plasma and primary information data, and to analyze the correlation between the changes in GST\u03b1 protein levels before and after the follow-up and cognitive function and its predictive value.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Plasma GST\u03b1 protein levels were significantly lower in the AD group than in the CN group (0.94 vs1.05, <jats:italic>p<\/jats:italic>\u202f=\u202f0.04) and the MCI group (0.94 vs1.09, <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001). Plasma GST\u03b1 protein level changes were positively correlated with altered MMSE levels in MCI and AD patients (<jats:italic>r<\/jats:italic>\u202f=\u202f0.09, <jats:italic>p<\/jats:italic>\u202f=\u202f0.04). The AUC (95% CI) of the area under the prediction curve of plasma GST\u03b1 protein levels for MCI was 0.63 (0.54\u20130.71), <jats:italic>p<\/jats:italic>\u202f=\u202f0.02, and the AUC (95% CI) of the area under the prediction curve of plasma GST\u03b1 protein levels for AD was 0.74 (0.69\u20130.80), <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001. At the same time, we plotted ROC curves for the difference in the change of plasma GST\u03b1 protein levels after 1\u202fyear of follow-up. The results showed that the AUC (95% CI) of the area under the prediction curve of plasma GST\u03b1 protein levels change for MCI was 0.76 (0.696\u20130.83), <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001, and the AUC (95% CI) of the area under the prediction curve of plasma GST\u03b1 protein levels change for AD was 0.75 (0.69\u20130.80), <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The findings of the study indicated notable differences in GST\u03b1 protein levels among patients with MCI and those with AD after a one-year follow-up period. Furthermore, a positive correlation was observed between changes in GST \u03b1protein levels and the decline in both baseline and cognitive function. This suggests that GST\u03b1 protein could potentially act as a biomarker for both MCI and AD, offering fresh insights for early detection and intervention strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2024.1517613","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T06:41:31Z","timestamp":1734936091000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Dynamic changes and prognostic value of glutathione S-transferase alpha in mild cognitive impairment and Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Yangyang","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyan","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingsheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"117957352092431","DOI":"10.1177\/1179573520924311","article-title":"Therapeutic potential of vitamin D and curcumin in anIn VitroModel of alzheimer disease","volume":"12","author":"Alamro","year":"2020","journal-title":"J. Cent. Nerv. Syst. Dis."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1750-1326-7-13","article-title":"Glutathione S-transferase omega genes in Alzheimer and Parkinson disease risk, age-at-diagnosis and brain gene expression: an association study with mechanistic implications","volume":"7","author":"Allen","year":"2012","journal-title":"Mol. Neurodegener."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"148134","DOI":"10.1016\/j.brainres.2022.148134","article-title":"Early time course of oxidative stress in hippocampal synaptosomes and cognitive loss following impaired insulin signaling in rats: development of sporadic Alzheimer\u2019s disease","volume":"1798","author":"Ansari","year":"2023","journal-title":"Brain Res."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1089\/rej.2010.1052","article-title":"Polymorphisms in glutathione S-transferase omega-1 gene and increased risk of sporadic Alzheimer disease","volume":"13","author":"Capurso","year":"2010","journal-title":"Rejuvenation Res."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"2767","DOI":"10.3390\/ijms24032767","article-title":"Protective effects of PEP-1-GSTA2 protein in hippocampal neuronal cell damage induced by oxidative stress","volume":"24","author":"Choi","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.pathophys.2018.06.001","article-title":"Genetic polymorphism of glutathione S-transferases: relevance to neurological disorders","volume":"25","author":"Dasari","year":"2018","journal-title":"Pathophysiology"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/S1474-4422(18)30403-4","article-title":"Global, regional, and national burden of Alzheimer\u2019s disease and other dementias, 1990-2016: a systematic analysis for the global burden of disease study 2016","volume":"18","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"3454","DOI":"10.3390\/nu15153454","article-title":"Polyphenols and their impact on the prevention of neurodegenerative diseases and development","volume":"15","author":"Grabska-Koby\u0142ecka","year":"2023","journal-title":"Nutrients"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1007\/s11064-020-02996-2","article-title":"Combination of omega 3 and coenzyme Q10 exerts neuroprotective potential against hypercholesterolemia-induced Alzheimer\u2019s-like disease in rats","volume":"45","author":"Ibrahim","year":"2020","journal-title":"Neurochem. Res."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2452","DOI":"10.4103\/1673-5374.339004","article-title":"Genetic dissection of glutathione S-transferase omega-1: identification of novel downstream targets and Alzheimer\u2019s disease pathways","volume":"17","author":"Jia","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1017\/S1041610217001120","article-title":"Differential associations between sensory loss and neuropsychiatric symptoms in adults with and without a neurocognitive disorder","volume":"30","author":"Kiely","year":"2018","journal-title":"Int. Psychogeriatr."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1080\/13543776.2017.1254192","article-title":"Role of glutathione-S-transferases in neurological problems","volume":"27","author":"Kumar","year":"2017","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"3259","DOI":"10.1093\/hmg\/ddg357","article-title":"Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease","volume":"12","author":"Li","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S0140-6736(20)30367-6","article-title":"Dementia prevention, intervention, and care: 2020 report of the lancet commission","volume":"396","author":"Livingston","year":"2020","journal-title":"Lancet (London, England)."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.1016\/S0140-6736(17)31363-6","article-title":"Dementia prevention, intervention, and care","volume":"390","author":"Livingston","year":"2017","journal-title":"Lancet (London, England)."},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics14121281","article-title":"Deep learning for Alzheimer\u2019s disease prediction: a comprehensive review","volume":"14","author":"Malik","year":"2024","journal-title":"Diagnostics"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"66","DOI":"10.12938\/bmfh.2021-067","article-title":"Sesame lignans upregulate glutathione S-transferase expression and downregulate microRNA-669c-3p","volume":"41","author":"Marugame","year":"2022","journal-title":"Biosci. Microbiota Food Health"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1002\/alz.12588","article-title":"Alzheimer\u2019s disease research progress in the Mediterranean region: the Alzheimer\u2019s Association international conference satellite symposium","volume":"18","author":"Sexton","year":"2022","journal-title":"Alzheimers Dement."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.mad.2004.08.029","article-title":"Glutathione S-transferase hGSTM3 and ageing-associated neurodegeneration: relationship to Alzheimer\u2019s disease","volume":"126","author":"Tchaikovskaya","year":"2005","journal-title":"Mech. Ageing Dev."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1007\/s10072-015-2245-7","article-title":"Glutathione S-transferases variants as risk factors in Alzheimer\u2019s disease","volume":"36","author":"Wang","year":"2015","journal-title":"Neurol. Sci."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e0260549","DOI":"10.1371\/journal.pone.0260549","article-title":"Risk and protective factors of neurocognitive disorders in older adults in central and Eastern Europe: a systematic review of population-based studies","volume":"16","author":"Wolfova","year":"2021","journal-title":"PloS one."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2022\/8287633","article-title":"Suppression of selective voltage-gated calcium channels alleviates neuronal degeneration and dysfunction through glutathione S-transferase-mediated oxidative stress resistance in a Caenorhabditis elegans model of Alzheimer\u2019s disease","volume":"2022","author":"Zheng","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"10389","DOI":"10.1109\/TPAMI.2024.3442811","article-title":"A new brain network construction paradigm for brain disorder via diffusion-based graph contrastive learning","volume":"46","author":"Zong","year":"2024","journal-title":"IEEE Trans. Pattern Anal. Mach. Intell."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"3652","DOI":"10.1109\/TCYB.2023.3344641","article-title":"Prior-guided adversarial learning with hypergraph for predicting abnormal connections in Alzheimer\u2019s disease","volume":"54","author":"Zuo","year":"2024","journal-title":"IEEE Trans. Cybern."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"4017","DOI":"10.1109\/TNSRE.2023.3323432","article-title":"Brain structure-function fusing representation learning using adversarial decomposed-VAE for analyzing MCI","volume":"31","author":"Zuo","year":"2023","journal-title":"IEEE Trans. Neural. Syst. Rehabil. 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