Genes最新文献

{"title":"Four Mitochondrial Genomes of Buprestinae (Coleoptera: Buprestidae) and Phylogenetic Analyses.","authors":"Yingying Li, Jieqiong Wang, Bowen Ouyang, Zhonghua Wei, Aimin Shi","doi":"10.3390/genes16070828","DOIUrl":"https://doi.org/10.3390/genes16070828","url":null,"abstract":"<p><strong>Background: </strong>The family Buprestidae is one of the largest families in Coleoptera; however, the number of reported mitochondrial genomes for this family is limited.</p><p><strong>Methods: </strong>In this study, mitogenomes of <i>Chrysobothris violacea</i>, <i>C. shirakii</i>, <i>Buprestis fairmairei,</i> and <i>Phaenops yin</i> were sequenced, assembled, and annotated. The mitogenomes of <i>Chrysobothris</i>, <i>Phaenops,</i> and <i>Buprestis</i> are reported for the first time.</p><p><strong>Results: </strong>The mitogenomes of <i>Chrysobothris violacea</i>, <i>C. shirakii</i>, and <i>Phaenops yin</i> are complete, while the mitogenome of <i>Buprestis fairmairei</i> is partial, lacking trnV and 12S genes. The AT-skew of these four mitogenomes is positive (0.02-0.09). Among the protein-coding genes, the Ka/Ks ratio for cox1 is the lowest (0.05), and the nucleotide diversity for nd6 is the highest.</p><p><strong>Conclusions: </strong>The phylogenetic trees based on mitogenome sequences suggest that the target genus <i>Chrysobothris</i> is sister to <i>Phaenops</i>, and the target genus <i>Buprestis</i> is sister to (<i>Melanophila</i> + (<i>Chrysobothris</i> + <i>Phaenops</i>)) clade. The results of this study will provide mitogenomic data for further research on the mitogenome and phylogeny of Buprestidae.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic Profiling of Gastric Cancer Reveals Key Biomarkers and Pathways via Bioinformatic Analysis.","authors":"Ipek Balikci Cicek, Zeynep Kucukakcali","doi":"10.3390/genes16070829","DOIUrl":"https://doi.org/10.3390/genes16070829","url":null,"abstract":"<p><strong>Background/objectives: </strong>Gastric cancer (GC) remains a significant global health burden due to its high mortality rate and frequent diagnosis at advanced stages. This study aimed to identify reliable diagnostic biomarkers and elucidate molecular mechanisms underlying GC by integrating transcriptomic data from independent platforms and applying machine learning techniques.</p><p><strong>Methods: </strong>Two transcriptomic datasets from the Gene Expression Omnibus were analyzed: GSE26899 (microarray, <i>n</i> = 108) as the discovery dataset and GSE248612 (RNA-seq, <i>n</i> = 12) for validation. Differential expression analysis was conducted using limma and DESeq2, selecting genes with |log2FC| > 1 and adjusted <i>p</i> < 0.05. The top 200 differentially expressed genes (DEGs) were used to develop machine learning models (random forest, logistic regression, neural networks). Functional enrichment analyses (GO, KEGG, Hallmark) were applied to explore relevant biological pathways.</p><p><strong>Results: </strong>In GSE26899, 627 DEGs were identified (201 upregulated, 426 downregulated), with key genes including <i>CST1</i>, <i>KIAA1199</i>, <i>TIMP1</i>, <i>MSLN</i>, and <i>ATP4A</i>. The random forest model demonstrated excellent classification performance (AUC = 0.952). GSE248612 validation yielded 738 DEGs. Cross-platform comparison confirmed 55.6% concordance among core genes, highlighting <i>CST1</i>, <i>TIMP1</i>, <i>KRT17</i>, <i>ATP4A</i>, <i>CHIA</i>, <i>KRT16</i>, and <i>CRABP2</i>. Enrichment analyses revealed involvement in ECM-receptor interaction, <i>PI3K-Akt</i> signaling, EMT, and cell cycle.</p><p><strong>Conclusions: </strong>This integrative transcriptomic and machine learning framework effectively identified high-confidence biomarkers for GC. Notably, <i>CST1</i>, <i>TIMP1</i>, <i>KRT16</i>, and <i>ATP4A</i> emerged as consistent, biologically relevant candidates with strong diagnostic performance and potential clinical utility. These findings may aid early detection strategies and guide future therapeutic developments in gastric cancer.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boosting Genomic Prediction Transferability with Sparse Testing.","authors":"Osval A Montesinos-López, Jose Crossa, Paolo Vitale, Guillermo Gerard, Leonardo Crespo-Herrera, Susanne Dreisigacker, Carolina Saint Pierre, Iván Delgado-Enciso, Abelardo Montesinos-López, Reka Howard","doi":"10.3390/genes16070827","DOIUrl":"https://doi.org/10.3390/genes16070827","url":null,"abstract":"<p><strong>Background/objectives: </strong>Improving sparse testing is essential for enhancing the efficiency of genomic prediction (GP). Accordingly, new strategies are being explored to refine genomic selection (GS) methods under sparse testing conditions.</p><p><strong>Methods: </strong>In this study, a sparse testing approach was evaluated, specifically in the context of predicting performance for tested lines in untested environments. Sparse testing is particularly practical in large-scale breeding programs because it reduces the cost and logistical burden of evaluating every genotype in every environment, while still enabling accurate prediction through strategic data use. To achieve this, we used training data from CIMMYT (Obregon, Mexico), along with partial data from India, to predict line performance in India using observations from Mexico.</p><p><strong>Results: </strong>Our results show that incorporating data from Obregon into the training set improved prediction accuracy, with greater effectiveness when the data were temporally closer. Across environments, Pearson's correlation improved by at least 219% (in a testing proportion of 50%), while gains in the percentage of matching in top 10% and 20% of top lines were 18.42% and 20.79%, respectively (also in a testing proportion of 50%).</p><p><strong>Conclusions: </strong>These findings emphasize that enriching training data with relevant, temporally proximate information is key to enhancing genomic prediction performance; conversely, incorporating unrelated data can reduce prediction accuracy.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detecting Methylation Changes Induced by Prime Editing.","authors":"Ronin Joshua S Cosiquien, Isaiah J Whalen, Phillip Wong, Ryan J Sorensen, Anala V Shetty, Shun-Qing Liang, Clifford J Steer","doi":"10.3390/genes16070825","DOIUrl":"https://doi.org/10.3390/genes16070825","url":null,"abstract":"<p><p>While prime editing offers improved precision compared to traditional CRISPR-Cas9 systems, concerns remain regarding potential off-target effects, including epigenetic changes such as DNA methylation. In this study, we investigated whether prime editing induces aberrant CpG methylation patterns. Whole-genome bisulfite sequencing revealed overall methylation similarity between Cas9-edited, and PE2-edited cells. However, localized epigenetic changes were observed, particularly in CpG islands and exon regions. The PE2-edited group showed a higher proportion of differentially methylated regions (DMRs) in some coding sequences compared to controls and Cas9-edited samples. Notably, CpG island methylation reached 0.18% in the PE2 vs. Cas9 comparison, indicating a higher susceptibility of these regulatory elements to epigenetic alterations by prime editing. Molecular function analyses including Gene Ontology and KEGG pathway analyses further revealed enrichment in molecular functions related to transcriptional regulation and redox activity in PE2-edited cells. These findings suggest that prime editing, while precise, may introduce subtle but functionally relevant methylation changes that could influence gene expression and cellular pathways. In summary, prime editing can induce localized DNA methylation changes in human cells, particularly within regulatory and coding regions. Understanding these epigenetic consequences is critical for the development of safer and more effective therapeutic applications of genome editing technologies.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Subset of HOX Genes Negatively Correlates with HOX/PBX Inhibitor Target Gene Expression and Is Associated with Apoptosis, DNA Repair, and Metabolism in Prostate Cancer.","authors":"Richard Morgan, Christopher Smith, Hardev Pandha","doi":"10.3390/genes16070824","DOIUrl":"https://doi.org/10.3390/genes16070824","url":null,"abstract":"<p><strong>Background/objectives: </strong>The <i>HOX</i> genes encode a family of homeodomain-containing transcription factors that have important roles in defining cell and tissue identity in embryonic development, but which also show deregulated expression in many cancers and have been shown to have pro-oncogenic roles. Due to their functionally redundant nature, strategies to target HOX protein function in cancer have focused on their interaction with their PBX cofactor using competitive peptides such as HXR9. HOX/PBX inhibition triggers apoptosis through a sudden increase in target gene expression, including <i>Fos</i>, <i>DUSP1</i>, and <i>ATF3</i>, which are otherwise repressed by HOX/PBX binding.</p><p><strong>Methods: </strong>We analyzed publicly available transcriptomic data in the R2 platform.</p><p><strong>Results: </strong>We show that a specific subgroup of <i>HOX</i> genes is negatively correlated with <i>Fos</i>, <i>DUSP1</i>, and <i>ATF3</i> expression in prostate cancer, and that this subgroup also shows a strong positive corelation with pathways that support tumour growth, most notably DNA repair and aminoacyl tRNA biosynthesis, and a negative correlation with genes that promote cell adhesion and prevent motility. In addition, this set of <i>HOX</i> genes strongly correlates with patient age, reflecting a previously identified progressive loss of regulation of <i>HOX</i> expression in normal peripheral blood cells.</p><p><strong>Conclusions: </strong>Our findings indicate these HOX genes may have pro-oncogenic functions in prostate cancer.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Imaging and Genomics in Amelogenesis Imperfecta: A Novel Diagnostic Approach.","authors":"Tina Leban, Aleš Fidler, Katarina Trebušak Podkrajšek, Alenka Pavlič, Tine Tesovnik, Barbara Jenko Bizjan, Blaž Vrhovšek, Robert Šket, Jernej Kovač","doi":"10.3390/genes16070822","DOIUrl":"https://doi.org/10.3390/genes16070822","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Amelogenesis imperfecta (AI) represents a heterogeneous group of inherited disorders affecting the quality and quantity of dental enamel, making clinical diagnosis challenging. This study aimed to identify genetic variants in Slovenian patients with non-syndromic AI and to evaluate enamel morphology using radiographic parameters. <b>Methods:</b> Whole exome sequencing (WES) was performed on 24 AI patients and their families. Panoramic radiographs (OPTs) were analyzed using Fiji ImageJ to assess crown dimensions, enamel angle (EA), dentine angle (DA), and enamel-dentine mineralization ratio (EDMR) in lower second molar buds, compared to matched controls (<i>n</i> = 24). Two observers independently assessed measurements, and non-parametric tests compared EA, DA, and EDMR in patients with and without disease-causing variants (DCVs). Statistical models, including bootstrap-validated random forest and logistic regression, assessed variable influences. <b>Results:</b> DCVs were identified in <i>ENAM</i> (40% of families), <i>AMELX</i> (15%), and <i>MMP20</i> (10%), including four novel variants. AI patients showed significant enamel deviations with high reproducibility, particularly in hypomineralized and hypoplastic regions. DA and EDMR showed significant correlations with DCVs (<i>p</i> < 0.01). A bootstrap-validated random forest model yielded a 90% (84.0-98.0%) AUC-estimated predictive power. <b>Conclusions:</b> These findings highlight a novel and reproducible radiographic approach for detecting developmental enamel defects in AI and support its diagnostic potential.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phylogenetic Analyses and Plastome Comparison to Confirm the Taxonomic Position of <i>Ligusticum multivittatum</i> (Apiaceae, Apioideae).","authors":"Changkun Liu, Boni Song, Feng Yong, Chengdong Xu, Quanying Dong, Xiaoyi Wang, Chao Sun, Zhenji Wang","doi":"10.3390/genes16070823","DOIUrl":"https://doi.org/10.3390/genes16070823","url":null,"abstract":"<p><strong>Background: </strong><i>Ligusticum</i> L. plants exhibit significant morphological variation in leaves, flowers, bracteoles and mericarps, thus the classifications of members for the genus have always been controversial. Among them, the taxonomic problem of <i>Ligusticum multivittatum</i> Franch. is the most prominent, which has not been sufficiently resolved so far.</p><p><strong>Methods: </strong>to clarify the taxonomic position of <i>Ligusticum multivittatum</i>, we performed phylogenetic analyses based on plastome data and ITS sequences. Meanwhile, we conducted comprehensively comparative plastome analyses between <i>Ligusticum multivittatum</i> and fifteen <i>Ligusticopsis</i> species.</p><p><strong>Results: </strong>Both analyses robustly supported that <i>Ligusticum multivittatum</i> nested in genus <i>Ligusticopsis</i> Leute and formed a clade with fifteen <i>Ligusticopsis</i> species, belonged to the Selineae tribe, which was distant from the type species of <i>Ligusticum</i> (<i>Ligusticum scoticum</i>), located in the <i>Acronema</i> clade.The comparative results showed that sixteen plastomes were highly similar and conservative in genome structure, size, gene content and arrangement, codon bias, SSRs and SC/IR. These findings imply that <i>Ligusticum multivittatum</i> is a member of <i>Ligusticopsis</i>, which was further verified by their shared morphological characters: stem base clothed in fibrous remnant sheaths, white petals, pinnate bracteoles, dorsally compressed mericarps with slightly prominent dorsal ribs, winged lateral ribs and numerous vittae in the commissure and in each furrow. Therefore, combining with the evidences of phylogenetic analyses, plastome comparison and morphological features, we affirmed that <i>Ligusticum multivittatum</i> indeed belonged to <i>Ligusticopsis</i> and transformed it into <i>Ligusticopsis</i> conducted by Pimenov was reasonable.</p><p><strong>Conclusions: </strong>Our study not only confirms the classification of <i>Ligusticum multivittatum</i> by integrating evidences, but also provides a reference for resolving taxonomy of contentious taxa.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of Gene Regulatory Networks Based on Spatial Multi-Omics Data and Application in Tumor-Boundary Analysis.","authors":"Yiwen Du, Kun Xu, Siwen Zhang, Lanming Chen, Zhenhao Liu, Lu Xie","doi":"10.3390/genes16070821","DOIUrl":"https://doi.org/10.3390/genes16070821","url":null,"abstract":"<p><strong>Background/objectives: </strong>Cell-cell communication (CCC) is a critical process within the tumor microenvironment, governing regulatory interactions between cancer cells and other cellular subpopulations. Aiming to improve the accuracy and completeness of intercellular gene-regulatory network inference, we constructed a novel spatial-resolved gene-regulatory network framework (spGRN).</p><p><strong>Methods: </strong>Firstly, the spatial multi-omics data of colorectal cancer (CRC) patients were analyzed. We precisely located the tumor boundaries and then systematically constructed the spGRN framework to study the network regulation. Subsequently, the key signaling molecules obtained by the spGRN were identified and further validated by the spatial-proteomics dataset.</p><p><strong>Results: </strong>Through the constructed spatial gene regulatory network, we found that in the communication with malignant cells, the highly expressed ligands <i>LIF</i> and <i>LGALS3BP</i> and receptors <i>IL6ST</i> and <i>ITGB1</i> in fibroblasts can promote tumor proliferation, and the highly expressed ligands <i>S100A8/S100A9</i> in plasma cells play an important role in regulating inflammatory responses. Further, validation of the key signaling molecules by the spatial-proteomics dataset highlighted the role of these genes in mediating the regulation of boundary-related cells. Furthermore, we applied the spGRN to publicly available single-cell and spatial-transcriptomics datasets from three other cancer types. The results demonstrate that ITGB1 and its target genes FOS/JUN were commonly expressed in all four cancer types, indicating their potential as pan-cancer therapeutic targets.</p><p><strong>Conclusion: </strong>the spGRN was proven to be a useful tool to select signal molecules as potential biomarkers or valuable therapeutic targets.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinician-Based Functional Scoring and Genomic Insights for Prognostic Stratification in Wolf-Hirschhorn Syndrome.","authors":"Julián Nevado, Raquel Blanco-Lago, Cristina Bel-Fenellós, Adolfo Hernández, María A Mori-Álvarez, Chantal Biencinto-López, Ignacio Málaga, Harry Pachajoa, Elena Mansilla, Fe A García-Santiago, Pilar Barrúz, Jair A Tenorio-Castaño, Yolanda Muñoz-GªPorrero, Isabel Vallcorba, Pablo Lapunzina","doi":"10.3390/genes16070820","DOIUrl":"https://doi.org/10.3390/genes16070820","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Wolf-Hirschhorn syndrome (WHS; OMIM #194190) is a rare neurodevelopmental disorder, caused by deletions in the distal short arm of chromosome 4. It is characterized by developmental delay, epilepsy, intellectual disability, and distinctive facial dysmorphism. Clinical presentation varies widely, complicating prognosis and individualized care. <b>Methods</b>: We assembled a cohort of 140 individuals with genetically confirmed WHS from Spain and Latin-America, and developed and validated a multidimensional, Clinician-Reported Outcome Assessment (ClinRO) based on the Global Functional Assessment of the Patient (GFAP), derived from standardized clinical questionnaires and weighted by HPO (Human Phenotype Ontology) term frequencies. The GFAP score quantitatively captures key functional domains in WHS, including neurodevelopment, epilepsy, comorbidities, and age-corrected developmental milestones (selected based on clinical experience and disease burden). <b>Results</b>: Higher GFAP scores are associated with worse clinical outcomes. GFAP showed strong correlations with deletion size, presence of additional genomic rearrangements, sex, and epilepsy severity. Ward's clustering and discriminant analyses confirmed GFAP's discriminative power, classifying over 90% of patients into clinically meaningful groups with different prognoses. <b>Conclusions</b>: Our findings support GFAP as a robust, WHS-specific ClinRO that may aid in stratification, prognosis, and clinical management. This tool may also serve future interventional studies as a standardized outcome measure. Beyond its clinical utility, GFAP also revealed substantial social implications. This underscores the broader socioeconomic burden of WHS and the potential value of GFAP in identifying high-support families that may benefit from targeted resources and services.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain and CSF Alzheimer's Biomarkers Are Associated with SERPINE1 Gene Expression.","authors":"Cynthia Picard, Henrik Zetterberg, Kaj Blennow, Sylvia Villeneuve, Judes Poirier, On Behalf Of The Prevent-Ad Research Group","doi":"10.3390/genes16070818","DOIUrl":"https://doi.org/10.3390/genes16070818","url":null,"abstract":"<p><strong>Background: </strong>SERPINE1, also known as plasminogen activator inhibitor (PAI), has been proposed as a potential blood biomarker for the early detection and diagnosis of Alzheimer's disease (AD). Expanding on previous studies, this research contrasted SERPINE1 levels in CSF and brain tissue of AD patients and those at risk for AD with established AD biomarkers.</p><p><strong>Methods: </strong>Utilizing OLINK and immunoassay methods, CSF SERPINE1 protein levels were quantified across two separate cohorts: PREVENT-AD and ADNI. Microarray and RNAseq were used to measure tissue <i>SERPINE1</i> mRNA levels in two separate cohorts: the Douglas-Bell Canada Brain Bank and the Mayo Clinic Brain Bank.</p><p><strong>Results: </strong>At the pre-clinical stage, elevated CSF levels of pTau, tTau and synaptic markers, alongside reduced hippocampal volume, correlate with CSF SERPINE1 levels. Elevated cortical <i>SERPINE1</i> mRNA levels in autopsy-confirmed AD show weak correlation with regional plaques and tangles densities, but strong correlation with Braak staging.</p><p><strong>Conclusions: </strong>CSF SERPINE1 levels can be used as an early biomarker for the detection of pathological changes associated with AD. Higher SERPINE1 levels correlate more strongly with tau pathology than with amyloid formation or deposition.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 7","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}