Journal of integrative neuroscience最新文献

{"title":"Applications and Possible Mechanisms of ULK4 in Brain: Implications for Neuropsychiatric Disorders.","authors":"Wen Luo, Jisheng Wang, Jing Chen","doi":"10.31083/JIN31350","DOIUrl":"https://doi.org/10.31083/JIN31350","url":null,"abstract":"<p><strong>Background: </strong>Neuropsychiatric disorders make up 14% of the global disease burden and are the leading cause of disability from noncommunicable diseases worldwide. The primary treatment for these disorders is drug therapy. Nonetheless, these therapies do not work completely for most patients, and even with attempts to create novel drugs, no medication has been confirmed as safe and effective for treating neuropsychiatric disorders. Recent studies have emphasized the role of gene therapy in neuropsychiatric disorders. Unc-51-like kinase (ULK) has connections to central nervous system functions and disorders, but the role of ULK4 is less well understood than other members of that family.</p><p><strong>Methods: </strong>The PubMed database was searched for articles regarding ULK4 in neuropsychiatric disorders and neurodevelopment with no restriction on publication date.</p><p><strong>Results: </strong>ULK4 is believed to function as a pseudokinase, potentially acting as a scaffold to connect kinases or other enzymes with their substrates or to manage the subcellular location of interacting proteins in different biological processes, abnormal low expression of which may increase the risk of neuropsychiatric disorders.</p><p><strong>Conclusions: </strong>This review updates the latest evidence on the roles of ULK4 in brain development and neuronal function, and highlights some controversies and uncertainties in the current research on ULK4. This review offers perspectives on the continuous development and design of drugs targeting ULK4, supporting possibilities for their future clinical application.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 5","pages":"31350"},"PeriodicalIF":2.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lamotrigine Enhances Autophagy and Reduces Post-Traumatic Spinal Neural Injury in Mice.","authors":"Mengting Zhang, Li Chen, Heren Gao, Tao Liu","doi":"10.31083/JIN37357","DOIUrl":"https://doi.org/10.31083/JIN37357","url":null,"abstract":"<p><strong>Background: </strong>Lamotrigine (LTG) is an antiepileptic drug that stabilizes the presynaptic membrane by blocking sodium channels and inhibiting excessive glutamate release. Its neuroprotective effects have been demonstrated in various pathological states. However, the role of LTG in spinal cord injury (SCI) and its relationship with autophagy, which is essential for cellular homeostasis, warrant further investigation.</p><p><strong>Methods: </strong>We established a mouse model of SCI using complete spinal transection. The neuroprotective effects of LTG were assessed using immunostaining and functional assessments, including Basso Mouse Scale (BMS) scores, lesion site area, and synapse survival. Western blot analyses were also performed to further examine the underlying cellular and molecular mechanisms of autophagy.</p><p><strong>Results: </strong>LTG treatment promoted the post-traumatic survival of spinal neurons, improved BMS scores, reduced lesion site area, and enhanced synapse survival in a mouse model of SCI. Furthermore, LTG attenuated apoptosis following SCI by activating autophagy during the secondary injury phase. These findings indicate that LTG-enhanced autophagosome formation and autolysosome degradation play a key role in reducing neuronal loss after SCI.</p><p><strong>Conclusion: </strong>LTG appears to attenuate post-traumatic spinal neural injury by enhancing autophagy flux.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 5","pages":"37357"},"PeriodicalIF":2.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal Imaging Markers of Cognitive Resilience and Molecular Mechanisms of Brain Resilience in Alzheimer's Disease.","authors":"Ze Yang, Jinhua Sheng, Qiao Zhang, Xiaoying Zhao, Yan Song, Guiguan Dong, Rong Zhang, Hongliang Zhao, Jialei Wang, Rong Pan, Haodi Zhu","doi":"10.31083/JIN26584","DOIUrl":"https://doi.org/10.31083/JIN26584","url":null,"abstract":"<p><p>Owing to the intricacy of the dementia course and the selection of clinical trial populations, research on distinct populations, comorbid conditions, and disease heterogeneity is currently a topic of great interest. For instance, more than 30% of individuals enlisted for natural history and clinical trial studies may exhibit pathology extending beyond Alzheimer's disease (AD). Additionally, recent autopsy studies have evinced significant heterogeneity in the neuropathology of individuals who succumb to dementia, with approximately 10%-30% of those clinically diagnosed with AD revealing no neurological lesions at autopsy. Nevertheless, 30%-40% of cognitively intact elderly individuals exhibit neurological lesions at autopsy. This indicates that the brain can withstand accumulated aging and neurological lesions while retaining brain integrity (brain resilience) or cognitive function (cognitive resilience). Presently, there is a lack of consensus on how to precisely define and measure the resilience of the brain and cognitive decline. This article encapsulates the research on constructing multimodal neuroimaging biomarkers for cognitive resilience, summarizes existing methods, and proposes some improvements. Furthermore, research findings on the biological mechanisms and genetic traits of brain resilience were collated, and the mechanisms for the formation of resilience and the genetic loci governing it were elucidated. Potential future research directions are also discussed.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 5","pages":"26584"},"PeriodicalIF":2.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation Analysis Between 3D and Plane DAT Binding Parameters of ¹¹C-CFT PET/CT and the Clinical Characteristics of Patients with Parkinson's Disease.","authors":"Xiaodong Wu, Ziyuan Li, Jing Gan, Feng Wei, Ping Wu, Sheng Liang, Yufei Ma, Lin Ding, Chuantao Zuo, Zhenguo Liu, Hui Wang, Yafu Yin","doi":"10.31083/JIN24440","DOIUrl":"https://doi.org/10.31083/JIN24440","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to investigate the correlation between dopamine transporter (DAT) positron emission tomography (PET)/computed tomography (CT) and the clinical characteristics and rating scales of Parkinson's disease (PD) patients. Additionally, we sought to assess the scientific validity and feasibility of integrating 3D-dopaminergic binding parameters into the clinical scoring system for PD.</p><p><strong>Methods: </strong>A total of 75 patients with PD who underwent ¹¹C-methyl-N-2β-methyl ester-3β-(4-fluorophenyl) tropane (¹¹C-CFT) PET/CT from April, 2019 to June, 2021 were retrospectively analyzed. Clinical characteristics, including age, sex, and disease duration, as well as the modified Hoehn-Yahr (H-Y) scale, Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III (II-III), and Mini-Mental State Examination (MMSE) scores of PD patients during the corresponding time periods were collected. DAT binding parameters and their derived parameters based on plane and 3D images in the neostriatum were analyzed for consistency with plane and 3D parameters, and the correlation between DAT parameters and the clinical features of patients were assessed using SPSS software.</p><p><strong>Results: </strong>The DAT binding parameters derived from 3D images demonstrated good consistency with the plane parameters (<i>p</i> < 0.05). The asymmetry index (ai) of DAT binding parameters based on 3D and plane images showed good consistency in the anterior putamen (<i>p</i> < 0.05). The plane parameters of the anterior and posterior putamen were statistically correlated with the UPDRS II-III score and H-Y score of PD patients (<i>p</i> < 0.05), whereas those of the caudate nucleus were correlated with UPDRS II and MMSE scores. The 3D parameters in the neostriatum showed good statistical correlation with disease duration, UPDRS II-III score, H-Y score, and H-Y stage of PD patients (<i>p</i> < 0.05), and the ai was significantly correlated with MMSE score (<i>p</i> < 0.05). The 3D parameters in the putamen and posterior putamen exhibited significant statistical correlation with the UPDRS II-III score, H-Y score, and H-Y stage in PD patients (<i>p</i> < 0.05). The ai in the putamen showed statistical correlation with UPDRS III and MMSE scores, and the ai in the posterior putamen showed statistical correlation with UPDRS II score (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>Quantitative parameters based on plane and 3D images of ¹¹C-CFT PET/CT showed good consistency. Moreover, 3D parameters in the neostriatum had a stronger correlation with activities of daily living, UPDRS motor scores, disease severity and duration, and cognition compared with plane parameters in PD patients.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 4","pages":"24440"},"PeriodicalIF":2.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Endovascular Revascularization on Functional Connectivity and Cognition in Symptomatic Chronic Internal Carotid Artery Occlusion Patients: A Preliminary Exploratory Study.","authors":"Renjie Ji, Shixin Zhang, Hanfeng Chen, Chunlan Deng, Ziqi Xu, Jie Zhang, Benyan Luo","doi":"10.31083/JIN36330","DOIUrl":"10.31083/JIN36330","url":null,"abstract":"<p><strong>Background: </strong>Symptomatic chronic internal carotid artery occlusion (CICAO) may lead to stroke and cognitive decline. Although endovascular recanalization has been proven to reduce the risk of future strokes, the effect on cognition remains controversial and requires further exploration. We explored alterations in functional connectivity (FC) and their associations with cognition in patients with symptomatic CICAO before and after carotid revascularization.</p><p><strong>Methods: </strong>Eighteen patients with unilateral CICAO and fifteen healthy controls (HCs) were enrolled. Resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological assessment were performed on all participants, before and after 6 months post-recanalization in the patient group. FC alterations in multiple brain networks and their correlations with cognitive scores were analyzed.</p><p><strong>Results: </strong>The FC of the CICAO group were markedly lower relative to the HC group for the following: the dorsal attention network (DAN) with the ipsilateral (occlusion side, right) middle frontal gyrus and frontal pole; the default mode network (DMN) with the ipsilateral angular gyrus; the visual network (VN) with the ipsilateral fusiform gyrus; and the frontoparietal network (FPN) with middle temporal gyrus on the side contralateral to the occlusion. The decreased FC of the DAN exhibited a positive association with the total score of the Mini-Mental State Examination (MMSE, r = 0.499, <i>p</i> = 0.049), Montreal Cognitive Assessment (MoCA, r = 0.515, <i>p</i> = 0.041), and Backward Digit Span Test (BDST, r = 0.594, <i>p</i> = 0.015), and negatively correlated with the score of Trail Making Test (TMT)-A (r = -0.563, <i>p</i> = 0.023) and TMT-B (r = -0.602, <i>p</i> = 0.014). The CICAO group exhibited significantly increased FC of the DMN seed region with the middle occipital gyrus ipsilateral to the occlusion. Additionally, the VN seed region demonstrated increased FC with the fusiform gyrus ipsilateral to the occlusion following endovascular recanalization. The preoperative FC values of the DMN exhibited a strong positive association with the improvement in TMT-A score (r = 0.629, <i>p</i> = 0.021).</p><p><strong>Conclusion: </strong>Our exploratory study found that FC disruption may induce cognitive decline in symptomatic CICAO patients. Endovascular recanalization may improve FC within key brain networks, supporting cognitive improvement. The baseline DMN FC was significantly associated with the postoperative improvement in TMT-A scores, suggesting that preoperative DMN FC could serve as a potential predictor of cognitive recovery.</p><p><strong>Clinical trial registration: </strong>NCT05292729. Registered 1 December 2021, https://clinicaltrials.gov/study/NCT05292729?intr=NCT05292729&rank=1.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 4","pages":"36330"},"PeriodicalIF":2.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis in Alzheimer's Disease: The Regulatory Role of Glial Cells.","authors":"Jingyi Xu, Rongjing Shen, Mengting Qian, Zhengjun Zhou, Bingqing Xie, Yong Jiang, Yang Yu, Wei Dong","doi":"10.31083/JIN25845","DOIUrl":"https://doi.org/10.31083/JIN25845","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disease characterized by the formation of amyloid plaques, neurofibrillary tangles and progressive cognitive decline. Amyloid-beta peptide (Aβ) monoclonal antibody therapeutic clinical trials have nearly failed, raising significant concerns about other etiological hypotheses about AD. Recent evidence suggests that AD patients also exhibit persistent neuronal loss and neuronal death accompanied by brain iron deposition or overload-related oxidative stress. Ferroptosis is a type of cell death that depends on iron, unlike autophagy and apoptosis. Inhibiting neuronal ferroptosis function is effective in improving cognitive impairment in AD. Notably, new research shows that ferroptosis in AD is crucially dependent on glial cell activation. This review examines the relationship between the imbalance of iron metabolism, the regulation of iron homeostasis in glial cells and neuronal death in AD pathology. Finally, the review summarizes some current drug research in AD targeting iron homeostasis, many novel iron-chelating compounds and natural compounds showing potential AD-modifying properties that may provide therapeutic targets for treating AD.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 4","pages":"25845"},"PeriodicalIF":2.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Cytokines in Postherpetic Neuralgia.","authors":"Yunyan Shen, Ping Lin","doi":"10.31083/JIN25829","DOIUrl":"https://doi.org/10.31083/JIN25829","url":null,"abstract":"<p><p>Nerve injury is a significant cause of postherpetic neuralgia (PHN). It is marked by upregulated expression of cytokines secreted by immune cells such as tumor necrosis factor alpha, interleukin 1 beta (IL-1β), IL-6, IL-18, and IL-10. In neuropathic pain (NP) due to nerve injury, cytokines are important for the induction of neuroinflammation, activation of glial cells, and expression of cation channels. The release of chemokines due to nerve injury promotes immune cell infiltration, recruiting inflammatory cytokines and further amplifying the inflammatory response. The resulting disequilibrium in neuroimmune response and neuroinflammation leads to a reduction of nerve fibers, altered nerve excitability, and neuralgia. PHN is a typical NP and cytokines may induce PHN by promoting central and peripheral sensitization. Currently, treating PHN is challenging and research on the role of cytokine signaling pathways in PHN is lacking. This review summarizes the potential mechanisms of cytokine-mediated PHN and discusses the cytokine signaling pathways associated with the central and peripheral sensitization of PHN. By elucidating the mechanisms of cytokines, the cells and molecules that regulate cytokines, and their signaling systems in PHN, this review reveals important research developments regarding cytokines and their signaling pathways mediating PHN, highlighting new targets of action for the development of analgesic drugs.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 4","pages":"25829"},"PeriodicalIF":2.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Therapeutics in the Treatment of Substance Use Disorders: A Focus on GLP-1 Receptor Agonists, D3R Antagonists, and CRF Antagonists.","authors":"Khaled Draghmeh, Brian Fuehrlein","doi":"10.31083/JIN26361","DOIUrl":"https://doi.org/10.31083/JIN26361","url":null,"abstract":"<p><p>The prevalence and rising use of alcohol, opioids, and stimulants have led to substance use disorders (SUDs) that are a significant public health challenge. Traditional treatments offer some benefit; however, they often limited by efficacy, side effects, and accessibility, highlighting the urgent need for novel therapeutics. This review explores the current literature surrounding three different classes of novel treatments: glucagon-like peptide-1 (GLP-1) receptor agonists, dopamine D3 receptor (D3R) antagonists, and corticotropin-releasing factor (CRF) antagonists. These therapeutics collectively target different aspects of the addiction process, such as stress and relapse prevention, reward modulation, and the reduction of drug-seeking behavior, leading to a combined multifaceted approach to treating SUDs. This review includes preclinical and clinical evidence supporting the use of these therapies, highlighting their potential to reduce substance use and prevent relapse to alcohol, opioid, and stimulant use. Despite the potentially promising findings of these treatments, further research is necessary to fully understand their mechanisms, optimize their application, and confirm their efficacy in clinical settings.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 4","pages":"26361"},"PeriodicalIF":2.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Static and Kinetic Disequilibrium are Central Neural Signs in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Therapeutic Effect of Repetitive Transcranial Magnetic Stimulation.","authors":"Kunihisa Miwa","doi":"10.31083/JIN25488","DOIUrl":"10.31083/JIN25488","url":null,"abstract":"<p><strong>Background: </strong>Chronic fatigue syndrome is primarily caused by myalgic encephalomyelitis (ME)-associated dysfunction of the central nervous system. Postural instability or disequilibrium is a typical neural sign and is classified as static or kinetic.</p><p><strong>Methods: </strong>A total of 160 ME patients (53 males and 107 females) with a mean age of 37 ± 12 years were enrolled in this study. They underwent both the Romberg test for static disequilibrium and the tandem gait test with turn and return for kinetic disequilibrium.</p><p><strong>Results: </strong>Static disequilibrium was found in 40 (25%) patients who showed instability when standing with both feet together and eyes either open (n = 7, 4%) or closed (n = 33, 21%). Kinetic disequilibrium was found in 71 (44%) patients, with 57 (36%) being positive for the straight tandem gait test. Fourteen (9%) patients were negative for the straight tandem gait test, but showed a positive result after turning and returning. Almost all patients with static disequilibrium also had kinetic disequilibrium (39/40, 98%). Patients with static and/or kinetic disequilibrium had a significantly higher prevalence of orthostatic intolerance, diagnosed as failure to complete the 10-min standing test, compared with patients without disequilibrium. They also had a significantly higher median performance status score (0-9) for restricted activities of daily living. Both types of disequilibria were recovered in 11 (85%) of 13 patients treated with repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex and primary motor area in the brain, suggesting a central vestibular origin.</p><p><strong>Conclusions: </strong>Static disequilibrium related to orthostatic intolerance, and kinetic disequilibrium related to gait disturbance are both prevalent in patients with ME and are important central neural signs that restrict activities of daily living. rTMS treatment effectively alleviated these disequilibria.</p><p><strong>Clinical trial registration: </strong>The study has been registered on https://jrct.mhlw.go.jp/ (registration number: jRCT1042240065; registration date: July 30, 2024).</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 4","pages":"25488"},"PeriodicalIF":2.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling of Circulating Cell-free DNA Methylation Patterns Identifies Aberrant Methylated <i>CTBP1</i> Promotor Sites for Prediction of Alzheimer's Disease.","authors":"Zhiwu Dong, Kewen Zhao, Hongjun Gu, Wenwei Yang, Xin Zhang","doi":"10.31083/JIN36527","DOIUrl":"https://doi.org/10.31083/JIN36527","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's 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.</p><p><strong>Methods: </strong>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 (<i>CTBP1</i>) 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.</p><p><strong>Results: </strong>A unique DNA methylation landscape in peripheral blood was characterized for AD patients and 4335 MVPs showed significant differential methylation (<i>p</i> < 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 <i>CTBP1</i> TSS1500 promoter showing significant differences when AD and controls were compared (<i>p</i> < 0.01), with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.779. Analysis of immune cell infiltration revealed <i>CTBP1</i> expression is significantly correlated with altered distribution of immune cells (<i>p</i> < 0.001), underscoring its potential role in modulating immune responses in AD. Moreover, <i>CTBP1</i> expression levels significantly varied across multiple GEO datasets.</p><p><strong>Conclusions: </strong>AD displays distinct DNA methylation patterns in peripheral blood and <i>CTBP1</i> promoter hypermethylation represents a promising potential biomarker for AD diagnosis.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 4","pages":"36527"},"PeriodicalIF":2.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}