EBioMedicine最新文献

{"title":"SARS-CoV-2 serotyping based on spike antigenicity and its implications for host immune evasion.","authors":"Wenjing Ruan, Pengyue Gao, Xiao Qu, Junlan Jiang, Zhennan Zhao, Shitong Qiao, He Zhang, Ting Yang, Dedong Li, Pei Du, Xuancheng Lu, Qihui Wang, Xin Zhao, George Fu Gao","doi":"10.1016/j.ebiom.2025.105634","DOIUrl":"10.1016/j.ebiom.2025.105634","url":null,"abstract":"<p><strong>Background: </strong>As SARS-CoV-2 continues to spread and evolve, new variants/sub-variants emerge, raising concerns about vaccine-induced immune escape. Here, we conducted a systematic analysis of the serology and immunogenicity of major circulating variants/sub-variants of SARS-CoV-2 since the outbreak.</p><p><strong>Methods: </strong>We expressed and purified trimeric S proteins from 21 SARS-CoV-2 variants, with SARS-CoV included as an outgroup. Mice were immunized, and the resulting antisera were tested for binding antibodies after the third dose injection, and for neutralizing antibodies (NAbs) after both the second and third doses. Using pseudovirus neutralization assays, we evaluated cross-neutralization among major circulating variants. By integrating serological classification, antigenic mapping, and 3D landscape analysis, we explored the antigenic relationships among different SARS-CoV-2 variants and their impact on serological responses.</p><p><strong>Findings: </strong>Based on the cross-neutralization activities of the sera from different S protein vaccinations and antigenicity analyses, we grouped the 21 lineages into six serotypes. Particularly, BA.2.86 and JN.1 had very weak cross-neutralization with all other SARS-CoV-2 sub-variants tested and were grouped into a separate serotype, Serotype VI.</p><p><strong>Interpretation: </strong>This systematic study contributes to a better understanding of the evolution of SARS-CoV-2 and its antigenic characteristics and provides valuable insights for vaccine development.</p><p><strong>Funding: </strong>This study was supported by the National Key R&D Program of China (2023YFC2307801, 2020YFA0509202 and 2021YFA1300803), the National Natural Science Foundation of China (82222040 and 82072289), CAS Project for Young Scientists in Basic Research (YSBR-083) and Beijing Nova Program of Science and Technology (20220484181).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105634"},"PeriodicalIF":9.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbapenem-resistant hypervirulent Klebsiella pneumoniae: where is it headed in the tug-of-war between virulence and resistance?","authors":"Meng Wang, Hui Wang","doi":"10.1016/j.ebiom.2025.105649","DOIUrl":"10.1016/j.ebiom.2025.105649","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105649"},"PeriodicalIF":9.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor telomeres and their magnitude of shortening post-allogeneic haematopoietic cell transplant impact survival for patients with early-stage leukaemia or myelodysplastic syndrome.","authors":"Shahinaz M Gadalla, Hormuzd A Katki, Tsung-Po Lai, Paul L Auer, Casey L Dagnall, Caitrin Bupp, Amy A Hutchinson, James J Anderson, Kyra J W Mendez, Stephen R Spellman, Valerie Stewart, Sharon A Savage, Stephanie J Lee, John E Levine, Wael Saber, Abraham Aviv","doi":"10.1016/j.ebiom.2025.105641","DOIUrl":"10.1016/j.ebiom.2025.105641","url":null,"abstract":"<p><strong>Background: </strong>Donor selection is a key success factor in allogeneic haematopoietic cell transplant (HCT). We evaluated the potential impact of donor leucocyte telomere length (LTL) and LTL shortening in recipients at three-month post-HCT (LTL-3MS) on the two-year HCT outcomes.</p><p><strong>Methods: </strong>We identified a cohort of 384 HCT recipients for early-stage leukaemia or myelodysplastic syndrome in the Blood and Marrow Transplant Clinical Trial Network protocol#1202 with blood samples collected three-month post-HCT. Blood samples from respective donors were available at the Centre for International Blood and Marrow Transplant Research biorepository. We used Cox proportional hazards models for statistical analyses.</p><p><strong>Findings: </strong>A better two-year overall survival (OS) was associated with longer donor LTL (adjusted-hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.37-0.96, for LTL ≥6.7 kb vs LTL< 6.7 kb, p = 0.03), and higher LTL-3MS (HR = 0.52, 95% CI = 0.34-0.80, for LTL-3MS ≥ 230 vs < 230 bp, p = 0.003). Longer donor LTL was associated with a lower risk of non-relapse mortality (NRM; HR = 0.48, p = 0.05), while higher LTL-3MS was associated with lower relapse risk (HR for relapse risk = 0.53, p = 0.008). The adjusted 2-year cumulative risk of all-cause mortality was reduced by about half for patients with both donor LTL ≥6.7 kb and LTL-3MS ≥ 230 bp vs patients with neither characteristic (21% vs 41%, respectively; p < 0.0001).</p><p><strong>Interpretation: </strong>Selection of donors with longer LTL may improve HCT outcomes. Limited LTL shortening in recipients post-HCT may guide relapse prediction.</p><p><strong>Funding: </strong>The NCI intramural research program and NIH grant U01AG066529.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105641"},"PeriodicalIF":9.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the role of small-molecule therapeutics for snake envenoming.","authors":"Anjana Silva, Geoffrey Isbister","doi":"10.1016/j.ebiom.2025.105635","DOIUrl":"10.1016/j.ebiom.2025.105635","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105635"},"PeriodicalIF":9.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular blueprint of healthy and diseased human epiglottis and subglottis-a study of the Canadian Airways Research (CARE) group.","authors":"Peter Y F Zeng, R Jun Lin, Kevin Fung, Halema Khan, Matthew J Cecchini, Elissa Woo, Amanda Hu, Jennifer Anderson, Patrick MacInnis, Laura Jarycki, Amir Karimi, Shengjie Ying, MohdWessam Al Jawhri, Sherman Lin, Mushfiq Shaikh, Harrison Pan, Bryan Coburn, Joe S Mymryk, Richard Inculet, John W Barrett, Anthony C Nichols","doi":"10.1016/j.ebiom.2025.105631","DOIUrl":"10.1016/j.ebiom.2025.105631","url":null,"abstract":"<p><strong>Background: </strong>The larynx consists of the supraglottis, glottis, and subglottis and each differ in tissue composition, lymphatic drainage, ability to counter infections, and response to injuries. However, the cellular mechanisms driving laryngeal homoeostasis remain largely unexplored. As a result, understanding disease pathogenesis within the larynx including idiopathic subglottic stenosis (iSGS) and intubation-related traumatic stenosis has been challenging. Here, we sought to characterise the cellular processes governing laryngeal health and disease.</p><p><strong>Methods: </strong>As part of the prospective Canadian Airways Research (CARE) iSGS study, we characterised 122,004 high-quality transcriptomes using single nucleus RNA-sequencing to profile 11 human epiglottis and 17 human subglottis biopsies across three different conditions: control, iSGS, and intubation-related traumatic stenosis to define cell populations and pathways associated with disease. We validated our results using cohort-level bulk transcriptomics using 114 human epiglottis and 121 human subglottis.</p><p><strong>Findings: </strong>We defined the single-cell taxonomy of the human subglottis and epiglottis using single-nucleus sequencing in both healthy and disease states. Mechanistically, we discovered the presence of unique epithelial and fibroblast progenitor subsets within the control subglottis but not within the anatomically adjacent epiglottis. The uncontrolled proliferation of these cellular subsets exhibited skewed sex hormone signalling and orchestrated a fibro-inflammatory cascade. We leveraged cohort-level bulk transcriptomics to define hallmarks of iSGS associated with disease covariates and introduced the first biomarker associated with recurrent relapse. Longitudinal sampling demonstrated that the subglottic microenvironment in patients with iSGS is changing dynamically with and without therapeutic intervention.</p><p><strong>Interpretation: </strong>Together, our data refines our understanding of laryngeal biology, nominates candidate compounds for iSGS treatment, and serves as a transformative platform for future clinical investigations to further precision laryngology.</p><p><strong>Funding: </strong>This study was funded by a grant from the American Laryngology Association (#1082), an Academic Medical Organisation of Southwestern Ontario innovation fund grant (INN21-016), grant support from the Departments of Otolaryngology-Head and Neck Surgery at University of Toronto, Canada and Western University, Canada. ACN was supported by the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers Fund. PYFZ was supported by a Vanier Canada Graduate Scholarship and PSI Foundation fellowship.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105631"},"PeriodicalIF":9.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cohort-level clinical trajectory and molecular landscape of idiopathic subglottic stenosis for precision laryngology-a study of the Canadian airways research (CARE) group.","authors":"R Jun Lin, Peter Yf Zeng, Kevin Fung, Halema Khan, Matthew J Cecchini, Elissa Woo, Amanda Hu, Jennifer Anderson, Patrick MacInnis, Amir Karimi, Shengjie Ying, MohdWessam Al Jawhri, Sherman Lin, Laura Jarycki, Mushfiq H Shaikh, Harrison Pan, Bryan Coburn, Joe S Mymryk, Richard Inculet, John W Barrett, Anthony C Nichols","doi":"10.1016/j.ebiom.2025.105629","DOIUrl":"10.1016/j.ebiom.2025.105629","url":null,"abstract":"<p><strong>Background: </strong>First described in 1972, idiopathic subglottic stenosis (iSGS) is a serious chronic orphan disease characterised by recurrent scarring of the subglottis. Although the cause is unknown, iSGS is almost exclusively restricted to Caucasian females typically in their fourth to sixth decade. However, given its rare incidence (1:400,000), understanding the clinical trajectory and molecular factors associated with iSGS disease development and prognosis has been difficult. In the current study we sought to unravel the pathogenesis of iSGS at the clinical, transcriptional, and genetic level in a prospective cohort.</p><p><strong>Methods: </strong>We prospectively enrolled 126 patients with iSGS, 104 controls, and 13 patients with traumatic SGS. Within this cohort, we profiled 114 human epiglottis and 121 human subglottis biopsies across three different conditions: control, iSGS, and intubation-related traumatic stenosis using bulk and single nucleus RNA-sequencing. Whole exome sequencing for germline variants was performed for 70 controls and 75 patients with iSGS.</p><p><strong>Findings: </strong>Patients with iSGS received a median number of five (range 0-18) surgical dilations at a rate of 1.031 dilations (range: 0.12-6.2) per year. Older age at diagnosis and higher Cotton-Myers grade were associated with increased number of surgical dilations over time. Cohort-level bulk transcriptomics found that iSGS pathology was restricted within the subglottis and did not affect anatomically adjacent epiglottis, opposite to previous hypotheses. We further identified cellular subsets associated with iSGS prognosis and severity. Finally, patients with iSGS exhibit lower testosterone predicted using a polygenic score.</p><p><strong>Interpretation: </strong>Together, our data refines our understanding of laryngeal biology and provides insights into the clinical trajectory of subglottic stenoses. Future research should explore the role of testosterone in the development of iSGS.</p><p><strong>Funding: </strong>This study was funded by a grant from the American Laryngology Association (#1082), an Academic Medical Organization of Southwestern Ontario innovation fund grant (INN21-016), grant support from the Departments of Otolaryngology-Head and Neck Surgery at University of Toronto and Western University. ACN was supported by the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers Fund. PYFZ was supported by a Vanier Canada Graduate Scholarship and PSI foundation fellowship.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105629"},"PeriodicalIF":9.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamics of gut resistome and mobilome in early life: a meta-analysis.","authors":"Ahmed Bargheet, Hanna Theodora Noordzij, Alise J Ponsero, Ching Jian, Katri Korpela, Mireia Valles-Colomer, Justine Debelius, Alexander Kurilshikov, Veronika Kuchařová Pettersen","doi":"10.1016/j.ebiom.2025.105630","DOIUrl":"10.1016/j.ebiom.2025.105630","url":null,"abstract":"<p><strong>Background: </strong>The gut microbiota of infants harbours a higher proportion of antibiotic resistance genes (ARGs) compared to adults, even in infants never exposed to antibiotics. Our study aims to elucidate this phenomenon by analysing how different perinatal factors influence the presence of ARGs, mobile genetic elements (MGEs), and their bacterial hosts in the infant gut.</p><p><strong>Methods: </strong>We searched MEDLINE and Embase up to April 3rd, 2023, for studies reporting infant cohorts with shotgun metagenomic sequencing of stool samples. The systematic search identified 14 longitudinal infant cohorts from 10 countries across three continents, featuring publicly available sequencing data with corresponding metadata. For subsequent integrative bioinformatic analyses, we used 3981 high-quality metagenomic samples from 1270 infants and 415 mothers.</p><p><strong>Findings: </strong>We identified distinct trajectories of the resistome and mobilome associated with birth mode, gestational age, antibiotic use, and geographical location. Geographical variation was exemplified by differences between cohorts from Europe, Southern Africa, and Northern America, which showed variation in both diversity and abundance of ARGs. On the other hand, we did not detect a significant impact of breastfeeding on the infants' gut resistome. More than half of detected ARGs co-localised with plasmids in key bacterial hosts, such as Escherichia coli and Enterococcus faecalis. These ARG-associated plasmids were gradually lost during infancy. We also demonstrate that E. coli role as a primary modulator of the infant gut resistome and mobilome is facilitated by its increased abundance and strain diversity compared to adults.</p><p><strong>Interpretation: </strong>Birth mode, gestational age, antibiotic exposure, and geographical location significantly influence the development of the infant gut resistome and mobilome. A reduction in E. coli relative abundance over time appears as a key factor driving the decrease in both resistome and plasmid relative abundance as infants grow.</p><p><strong>Funding: </strong>Centre for Advanced Study in Oslo, Norway. Centre for New Antibacterial Strategies through the Tromsø Research Foundation, Norway.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105630"},"PeriodicalIF":9.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid high-throughput sequencing: a game-changer for timely addressing infectious diseases.","authors":"Hui Tang, Dongsheng Han","doi":"10.1016/j.ebiom.2025.105639","DOIUrl":"10.1016/j.ebiom.2025.105639","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"114 ","pages":"105639"},"PeriodicalIF":9.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19: an international, randomised, open-label trial.","authors":"Simone Hoffmann, Eva Schrezenmeier, Maxime Desmarets, Fabian Halleck, Antoine Durrbach, Lynn Peters, Anna-Teresa Tremmel, Alina Seidel, Marita Führer, Friederike Bachmann, Jens Schrezenmeier, Jochen Greiner, Sixten Körper, Henrike Hofmann, Carolin Ludwig, Christiane Vieweg, Bernd Jahrsdörfer, Klemens Budde, Michael Schmidt, Jan Münch, Nizar Joher, Etienne Daguindau, Beate Grüner, Gaëlle Brunotte, Charline Vauchy, Erhard Seifried, Daniel Bradshaw, Lise J Estcourt, David J Roberts, Eric Toussirot, Bart Rijnders, Pierre Tiberghien, Hubert Schrezenmeier","doi":"10.1016/j.ebiom.2025.105613","DOIUrl":"10.1016/j.ebiom.2025.105613","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 convalescent plasma (CCP) is a treatment option for COVID-19. This study investigated the safety and efficacy of early, very high-titre CCP in immunocompromised individuals with mild COVID-19.</p><p><strong>Methods: </strong>This randomised, controlled, open-label trial assessed CCP in immunocompromised patients (n = 120) with mild COVID-19 in 10 clinical trial centres across Germany, France, and the Netherlands. Patients were randomised 1:1 to receive either standard of care (SoC) alone (SoC group) or SoC and 2 units of CCP. Most patients (89.7%) had received ≥3 SARS-CoV-2 vaccinations. The primary endpoint was hospitalisation for progressive COVID-19 symptoms or death by day 28 after randomisation, analysed on a modified intention-to-treat basis (117 patients). The safety analysis included the full analysis set. The trial is registered with EudraCT 2021-006621-22, and ClinicalTrials.gov, NCT05271929.</p><p><strong>Findings: </strong>Between April 11, 2022 and November 27, 2023, 120 patients were enrolled. Patients in the CCP group received a median of 559 ml CCP from convalescent, vaccinated donors with very high levels of SARS-CoV-2 antibodies (median 81,810 IU/ml) at a median 4 days after symptom onset. The primary outcome occurred in 5/58 patients (8.6%) in the SoC group and in 0/59 patients (0%) in the CCP group, difference -8.6% (95% confidence interval of difference -19% to -0.80%; p-value 0.027; Fisher's exact test). The course of SARS-CoV-2 antibodies in the patients demonstrated a passive transfer of antibodies by the CCP, in particular neutralising effects against new SARS-CoV-2 variants. Whole genome sequencing of SARS-CoV-2 in patients during follow-up showed significant intra-host viral evolution, but without differences between groups. CCP was well tolerated.</p><p><strong>Interpretation: </strong>Early administration of high-titre CCP can prevent hospitalisation or death in immunocompromised patients with mild COVID-19.</p><p><strong>Funding: </strong>Support-e project (European Union's Horizon 2020 Programme), German Federal Ministry of Education and Research, ZonMw, the Netherlands Organisation for Health Research and Development.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"113 ","pages":"105613"},"PeriodicalIF":9.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11919330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ten years preceding a diagnosis of neurodegenerative disease in Europe and Australia: medication use, health conditions, and biomarkers associated with Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.","authors":"Dang Wei, Anna Freydenzon, Octave Guinebretiere, Karim Zaidi, Fen Yang, Weimin Ye, Niklas Hammar, Karin Modig, Naomi R Wray, Maria Feychting, Nadine Hamieh, Bruno Ventelou, Beranger Lekens, Laurene Gantzer, Stanley Durrleman, Allan McRae, Baptiste Couvy-Duchesne, Fang Fang, Thomas Nedelec","doi":"10.1016/j.ebiom.2025.105585","DOIUrl":"10.1016/j.ebiom.2025.105585","url":null,"abstract":"<p><strong>Background: </strong>Many studies have investigated early predictors for Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). However, evidence is sparse regarding specific and common predictors for these diseases. We aimed to identify medication use, health conditions, and blood biomarkers that might be associated with the risk of AD, PD, and ALS ten years later.</p><p><strong>Methods: </strong>We conducted population-based nested case-control studies of AD, PD, and ALS using electronic medical records in Europe (France, the UK, and Sweden) and Australia. We retrieved data on medication use, diagnosed health conditions, and measured blood biomarkers from electronic medical records or biomedical cohorts. Conditional logistic regression models and meta-analysis were applied to assess the associations between these factors and the risk of receiving a diagnosis of AD, PD, or ALS.</p><p><strong>Findings: </strong>We included a total of 149,642 AD cases (mean age: 79.1-81.2 years), 252,696 PD cases (73.2-75.9 years), and 27,533 ALS cases (64.4-69.6 years). The prescription of psychoanaleptics and nasal preparations was consistently associated with an increased risk of AD, PD, and ALS 5-10 years later. Constipation and use of related medications were associated with an increased risk of AD and PD, while diabetes and use of antidiabetics were associated with a reduced risk of ALS. A higher level of triglycerides was associated with a lower risk of AD, whereas a higher level of Apolipoprotein B was associated with a lower risk of PD, 5-10 years later.</p><p><strong>Interpretation: </strong>Psychoanaleptics and nasal preparations may serve as common predictors for diagnosis of AD, PD, and ALS 5-10 years later. Conversely, the increased prevalence of constipation is specific to AD and PD, while the decreased prevalence of diabetes and use of antidiabetics is specific to ALS.</p><p><strong>Funding: </strong>EU Joint Programme-Neurodegenerative Disease Research.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"113 ","pages":"105585"},"PeriodicalIF":9.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}