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Integr. Neurosci."],"abstract":"<jats:p>Background: Alzheimer\u2019s disease (AD) is the most common neurodegenerative disease affecting the elderly, with its diagnosis at early stages crucial for effective intervention. Recent evidence increasingly supports the role of epigenetic alterations in AD pathogenesis, highlighting the need for innovative biomarkers that reflect these changes. This study aimed to characterize the genome-wide DNA methylation profiles of cell-free DNA in peripheral blood for potential biomarkers associated with AD. Methods: The Illumina Infinium array was utilized to detect the methylation patterns of circulating cell-free DNA from AD patients and healthy controls. The R Bioconductor Linear Models for Microarray Data (LIMMA) package was employed to identify methylation variable positions (MVPs), and Probe Lasso was used to pinpoint differentially methylated regions (DMRs) linked to AD. Bioinformatics enrichment analysis of the annotated genes was performed using EnrichR. A second cohort was recruited to validate the methylation changes at the C-terminal binding protein1 (CTBP1) promoter cytosine-phosphate-guanine (CpG) sites via pyrosequencing. Additionally, microarray data from the Gene Expression Omnibus (GEO) database were analyzed to further validate gene expression and immune infiltration. Results: A unique DNA methylation landscape in peripheral blood was characterized for AD patients and 4335 MVPs showed significant differential methylation (p &lt; 0.01). Functional annotation and pathway enrichment analysis underscored processes and pathways inherent in the nervous system. Probe Lasso identified 68 DMRs annotated to 10 genes, with hypermethylation of CpG islands in the CTBP1 TSS1500 promoter showing significant differences when AD and controls were compared (p &lt; 0.01), with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.779. Analysis of immune cell infiltration revealed CTBP1 expression is significantly correlated with altered distribution of immune cells (p &lt; 0.001), underscoring its potential role in modulating immune responses in AD. Moreover, CTBP1 expression levels significantly varied across multiple GEO datasets. Conclusions: AD displays distinct DNA methylation patterns in peripheral blood and CTBP1 promoter hypermethylation represents a promising potential biomarker for AD diagnosis.<\/jats:p>","DOI":"10.31083\/jin36527","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T05:53:52Z","timestamp":1745992432000},"source":"Crossref","is-referenced-by-count":1,"title":["Profiling of Circulating Cell-free DNA Methylation Patterns Identifies Aberrant Methylated CTBP1 Promotor Sites for Prediction of Alzheimer\u2019s Disease"],"prefix":"10.31083","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3792-9556","authenticated-orcid":true,"given":"Zhiwu","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Shanghai Second People\u2019s Hospital, 200011 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3135-1607","authenticated-orcid":true,"given":"Kewen","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9068-1328","authenticated-orcid":true,"given":"Hongjun","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Geriatric Medicine, Shanghai Jinshan District Hospital of Integrated Traditional Chinese and Western Medicine, 201501 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3227-2783","authenticated-orcid":true,"given":"Wenwei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Shanghai Second People\u2019s Hospital, 200011 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9186-9402","authenticated-orcid":true,"given":"Xin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Shanghai Second People\u2019s Hospital, 200011 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Jack CR, Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease. Alzheimer\u2019s & Dementia: the Journal of the Alzheimer\u2019s Association. 2018; 14: 535\u2013562.","DOI":"10.1016\/j.jalz.2018.02.018."},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Bos I, Vos S, Verhey F, Scheltens P, Teunissen C, Engelborghs S, et al. Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer\u2019s disease spectrum. Alzheimer\u2019s & Dementia: the Journal of the Alzheimer\u2019s Association. 2019; 15: 644\u2013654.","DOI":"10.1016\/j.jalz.2019.01.004."},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Gordon BA, Blazey TM, Su Y, Hari-Raj A, Dincer A, Flores S, et al. Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer\u2019s disease: a longitudinal study. Lancet Neurology. 2018; 17: 241\u2013250.","DOI":"10.1016\/S1474-4422(18)30028-0."},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Rabinovici GD, Gatsonis C, Apgar C, Chaudhary K, Gareen I, Hanna L, et al. Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia. JAMA. 2019; 321: 1286\u20131294.","DOI":"10.1001\/jama.2019.2000."},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Nakamura A, Kaneko N, Villemagne VL, Kato T, Doecke J, Dor\u00e9 V, et al. High performance plasma amyloid-\u03b2 biomarkers for Alzheimer\u2019s disease. Nature. 2018; 554: 249\u2013254.","DOI":"10.1038\/nature25456."},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Park JC, Han SH, Yi D, Byun MS, Lee JH, Jang S, et al. Plasma tau\/amyloid-\u03b21-42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer\u2019s disease. Brain: a Journal of Neurology. 2019; 142: 771\u2013786.","DOI":"10.1093\/brain\/awy347."},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Karikari TK, Pascoal TA, Ashton NJ, Janelidze S, Benedet AL, Rodriguez JL, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer\u2019s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. The Lancet. Neurology. 2020; 19: 422\u2013433.","DOI":"10.1016\/S1474-4422(20)30071-5."},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Dong Z, Gu H, Guo Q, Liang S, Xue J, Yao F, et al. Profiling of Serum Exosome MiRNA Reveals the Potential of a MiRNA Panel as Diagnostic Biomarker for Alzheimer\u2019s Disease. Molecular Neurobiology. 2021; 58: 3084\u20133094.","DOI":"10.1007\/s12035-021-02323-y."},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Dubois B, Villain N, Frisoni GB, Rabinovici GD, Sabbagh M, Cappa S, et al. Clinical diagnosis of Alzheimer\u2019s disease: recommendations of the International Working Group. The Lancet. Neurology. 2021; 20: 484\u2013496.","DOI":"10.1016\/S1474-4422(21)00066-1."},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Cavalli G, Heard E. Advances in epigenetics link genetics to the environment and disease. Nature. 2019; 571: 489\u2013499.","DOI":"10.1038\/s41586-019-1411-0."},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Greenberg MVC, Bourc\u2019his D. The diverse roles of DNA methylation in mammalian development and disease. Nature Reviews. Molecular Cell Biology. 2019; 20: 590\u2013607.","DOI":"10.1038\/s41580-019-0159-6."},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Robertson KD. DNA methylation and human disease. Nature Reviews. Genetics. 2005; 6: 597\u2013610.","DOI":"10.1038\/nrg1655."},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Gasparoni G, Bultmann S, Lutsik P, Kraus TFJ, Sordon S, Vlcek J, et al. DNA methylation analysis on purified neurons and glia dissects age and Alzheimer\u2019s disease-specific changes in the human cortex. Epigenetics & Chromatin. 2018; 11: 41.","DOI":"10.1186\/s13072-018-0211-3."},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Altuna M, Urd\u00e1noz-Casado A, S\u00e1nchez-Ruiz de Gordoa J, Zelaya MV, Labarga A, Lepesant JMJ, et al. DNA methylation signature of human hippocampus in Alzheimer\u2019s disease is linked to neurogenesis. Clinical Epigenetics. 2019; 11: 91.","DOI":"10.1186\/s13148-019-0672-7."},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Wei X, Du P, Zhao Z. Impacts of DNA methylation on Tau protein related genes in the brains of patients with Alzheimer\u2019s disease. Neuroscience Letters. 2021; 763: 136196.","DOI":"10.1016\/j.neulet.2021.136196."},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Sanchez-Mut JV, Aso E, Heyn H, Matsuda T, Bock C, Ferrer I, et al. Promoter hypermethylation of the phosphatase DUSP22 mediates PKA-dependent TAU phosphorylation and CREB activation in Alzheimer\u2019s disease. Hippocampus. 2014; 24: 363\u2013368.","DOI":"10.1002\/hipo.22245."},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Monti N, Cavallaro RA, Stoccoro A, Nicolia V, Scarpa S, Kovacs GG, et al. CpG and non-CpG Presenilin1 methylation pattern in course of neurodevelopment and neurodegeneration is associated with gene expression in human and murine brain. Epigenetics. 2020; 15: 781\u2013799.","DOI":"10.1080\/15592294.2020.1722917."},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Kobayashi N, Shinagawa S, Niimura H, Kida H, Nagata T, Tagai K, et al. Increased blood COASY DNA methylation levels a potential biomarker for early pathology of Alzheimer\u2019s disease. Scientific Reports. 2020; 10: 12217.","DOI":"10.1038\/s41598-020-69248-9."},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Hu H, Tan L, Bi YL, Xu W, Tan L, Shen XN, et al. Association between methylation of BIN1 promoter in peripheral blood and preclinical Alzheimer\u2019s disease. Translational Psychiatry. 2021; 11: 89.","DOI":"10.1038\/s41398-021-01218-9."},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Li QS, Vasanthakumar A, Davis JW, Idler KB, Nho K, Waring JF, et al. Association of peripheral blood DNA methylation level with Alzheimer\u2019s disease progression. Clinical Epigenetics. 2021; 13: 191.","DOI":"10.1186\/s13148-021-01179-2."},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Ma SL, Tang NLS, Lam LCW. Promoter Methylation and Gene Expression of Pin1 Associated with the Risk of Alzheimer\u2019s Disease in Southern Chinese. Current Alzheimer Research. 2020; 17: 1232\u20131237.","DOI":"10.2174\/1567205018666210208163946."},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Guemri J, Pierre-Jean M, Brohard S, Oussada N, Horgues C, Bonnet E, et al. Methylated ccfDNA from plasma biomarkers of Alzheimer\u2019s disease using targeted bisulfite sequencing. Epigenomics. 2022; 14: 451\u2013468.","DOI":"10.2217\/epi-2021-0491."},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Chinnadurai G. Transcriptional regulation by C-terminal binding proteins. The International Journal of Biochemistry & Cell Biology. 2007; 39: 1593\u20131607.","DOI":"10.1016\/j.biocel.2007.01.025."},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Dahiya A, Wong S, Gonzalo S, Gavin M, Dean DC. Linking the Rb and polycomb pathways. Molecular Cell. 2001; 8: 557\u2013569.","DOI":"10.1016\/s1097-2765(01)00346-x."},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Wang L, Guo S, Cao K, Li Z, Li Z, Song M, et al. Glycolysis Promotes Angiotensin II-Induced Aortic Remodeling Through Regulating Endothelial-to-Mesenchymal Transition via the Corepressor C-Terminal Binding Protein 1. Hypertension (Dallas, Tex.: 1979). 2023; 80: 2627\u20132640.","DOI":"10.1161\/HYPERTENSIONAHA.123.21382."},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Chinnadurai G. CtBP, an unconventional transcriptional corepressor in development and oncogenesis. Molecular Cell. 2002; 9: 213\u2013224.","DOI":"10.1016\/s1097-2765(02)00443-4."},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Riefler GM, Firestein BL. Binding of neuronal nitric-oxide synthase (nNOS) to carboxyl-terminal-binding protein (CtBP) changes the localization of CtBP from the nucleus to the cytosol: a novel function for targeting by the PDZ domain of nNOS. The Journal of Biological Chemistry. 2001; 276: 48262\u201348268.","DOI":"10.1074\/jbc.M106503200."},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Stankiewicz TR, Gray JJ, Winter AN, Linseman DA. C-terminal binding proteins: central players in development and disease. Biomolecular Concepts. 2014; 5: 489\u2013511.","DOI":"10.1515\/bmc-2014-0027."},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Li X, Bai Z, Li Z, Wang J, Yan X. Toosendanin Restrains Idiopathic Pulmonary Fibrosis by Inhibiting ZEB1\/CTBP1 Interaction. Current Molecular Medicine. 2024; 24: 123\u2013133.","DOI":"10.2174\/1566524023666230501205149."},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Serra-Almeida C, Saraiva C, Esteves M, Ferreira R, Santos T, Crist\u00f3v\u00e3o AC, et al. C-Terminal Binding Proteins Promote Neurogenesis and Oligodendrogenesis in the Subventricular Zone. Frontiers in Cell and Developmental Biology. 2021; 8: 584220.","DOI":"10.3389\/fcell.2020.584220."},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Saraiva C, Lopes-Nunes J, Esteves M, Santos T, Vale A, Crist\u00f3v\u00e3o AC, et al. CtBP Neuroprotective Role in Toxin-Based Parkinson\u2019s Disease Models: From Expression Pattern to Dopaminergic Survival. Molecular Neurobiology. 2023; 60: 4246\u20134260.","DOI":"10.1007\/s12035-023-03331-w."},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Stankiewicz TR, Schroeder EK, Kelsey NA, Bouchard RJ, Linseman DA. 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The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease. Alzheimer\u2019s & Dementia: the Journal of the Alzheimer\u2019s Association. 2011; 7: 263\u2013269.","DOI":"10.1016\/j.jalz.2011.03.005."},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Teschendorff AE, Marabita F, Lechner M, Bartlett T, Tegner J, Gomez-Cabrero D, et al. A beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450 k DNA methylation data. Bioinformatics (Oxford, England). 2013; 29: 189\u2013196.","DOI":"10.1093\/bioinformatics\/bts680."},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research. 2015; 43: e47.","DOI":"10.1093\/nar\/gkv007."},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Butcher LM, Beck S. Probe Lasso: a novel method to rope in differentially methylated regions with 450K DNA methylation data. Methods (San Diego, Calif.). 2015; 72: 21\u201328.","DOI":"10.1016\/j.ymeth.2014.10.036."},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Song H, Yang J, Yu W. Promoter Hypomethylation of TGFBR3 as a Risk Factor of Alzheimer\u2019s Disease: An Integrated Epigenomic-Transcriptomic Analysis. Frontiers in Cell and Developmental Biology. 2022; 9: 825729.","DOI":"10.3389\/fcell.2021.825729."},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Vejandla B, Savani S, Appalaneni R, Veeravalli RS, Gude SS. Alzheimer\u2019s Disease: The Past, Present, and Future of a Globally Progressive Disease. Cureus. 2024; 16: e51705.","DOI":"10.7759\/cureus.51705."},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Yokoyama AS, Rutledge JC, Medici V. DNA methylation alterations in Alzheimer\u2019s disease. Environmental Epigenetics. 2017; 3: dvx008.","DOI":"10.1093\/eep\/dvx008."},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Sun X, Xiao L, Chen J, Chen X, Chen X, Yao S, et al. DNA methylation is involved in the pathogenesis of osteoarthritis by regulating CtBP expression and CtBP-mediated signaling. International Journal of Biological Sciences. 2020; 16: 994\u20131009.","DOI":"10.7150\/ijbs.39945."},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Zeng J, Chen JY, Meng J, Chen Z. Inflammation and DNA methylation coregulate the CtBP-PCAF-c-MYC transcriptional complex to activate the expression of a long non-coding RNA CASC2 in acute pancreatitis. International Journal of Biological Sciences. 2020; 16: 2116\u20132130.","DOI":"10.7150\/ijbs.43557."},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Hu K, Li Y, Yu H, Hu Y. CTBP1 Confers Protection for Hippocampal and Cortical Neurons in Rat Models of Alzheimer\u2019s Disease. Neuroimmunomodulation. 2019; 26: 139\u2013152.","DOI":"10.1159\/000500942."},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Chinnadurai G. CtBP family proteins: more than transcriptional corepressors. BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology. 2003; 25: 9\u201312.","DOI":"10.1002\/bies.10212."},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"H\u00fcbler D, Rankovic M, Richter K, Lazarevic V, Altrock WD, Fischer KD, et al. Differential spatial expression and subcellular localization of CtBP family members in rodent brain. 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