EBioMedicine最新文献

{"title":"Linking obesity-associated genotype to child language development: the role of early-life neurology-related proteomics and brain myelination.","authors":"Jian Huang, Jinyi Che, Michelle Z L Kee, Ai Peng Tan, Evelyn C Law, Patricia Pelufo Silveira, Irina Pokhvisneva, Sachin Patel, Keith M Godfrey, Lourdes Mary Daniel, Kok Hian Tan, Yap Seng Chong, Shiao-Yng Chan, Johan G Eriksson, Dennis Wang, Jonathan Yinhao Huang","doi":"10.1016/j.ebiom.2025.105579","DOIUrl":"10.1016/j.ebiom.2025.105579","url":null,"abstract":"<p><strong>Background: </strong>The association between childhood obesity and language development may be confounded by socio-environmental factors and attributed to comorbid pathways.</p><p><strong>Methods: </strong>In a longitudinal Singaporean mother-offspring cohort, we leveraged trans-ancestry polygenic predictions of body mass index (BMI) to interrogate the causal effects of early-life BMI on child language development and its effects on molecular and neuroimaging measures. Leveraging large genome-wide association studies, we examined whether the link between obesity and language development is causal or due to a shared genetic basis.</p><p><strong>Findings: </strong>We found an inverse association between polygenic risk for obesity, which is less susceptible to confounding, and language ability assessed at age 9. Our findings suggested a shared genetic basis between obesity and language development rather than a causal effect of obesity on language development. Interrogating early-life mechanisms including neurology-related proteomics and language-related white matter microstructure, we found that EFNA4 and VWC2 expressions were associated with language ability as well as fractional anisotropy of language-related white matter tracts, suggesting a role in brain myelination. Additionally, the expression of the EPH-Ephrin signalling pathway in the hippocampus might contribute to language development. Polygenic risk for obesity was nominally associated with EFNA4 and VWC2 expression. However, we did not find support for mediating mechanisms via these proteins.</p><p><strong>Interpretation: </strong>This study demonstrates the potential of examining early-life proteomics in conjunction with deep genotyping and phenotyping and provides biological insights into the shared genomic links between obesity and language development.</p><p><strong>Funding: </strong>Singapore National Research Foundation and Agency for Science, Technology and Research.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"113 ","pages":"105579"},"PeriodicalIF":9.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406400","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":"Revolutionizing CRISPR-based RNA diagnostics with single nucleotide resolution.","authors":"Hongyan Liu, Leshan Xiu, Qing Yun Li, Kun Yin","doi":"10.1016/j.ebiom.2025.105617","DOIUrl":"10.1016/j.ebiom.2025.105617","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"113 ","pages":"105617"},"PeriodicalIF":9.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467327","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":"Machine learning detection of heteroresistance in Escherichia coli.","authors":"Andrei Guliaev, Karin Hjort, Michele Rossi, Sofia Jonsson, Hervé Nicoloff, Lionel Guy, Dan I Andersson","doi":"10.1016/j.ebiom.2025.105618","DOIUrl":"10.1016/j.ebiom.2025.105618","url":null,"abstract":"<p><strong>Background: </strong>Heteroresistance (HR) is a significant type of antibiotic resistance observed for several bacterial species and antibiotic classes where a susceptible main population contains small subpopulations of resistant cells. Mathematical models, animal experiments and clinical studies associate HR with treatment failure. Currently used susceptibility tests do not detect heteroresistance reliably, which can result in misclassification of heteroresistant isolates as susceptible which might lead to treatment failure. Here we examined if whole genome sequence (WGS) data and machine learning (ML) can be used to detect bacterial HR.</p><p><strong>Methods: </strong>We classified 467 Escherichia coli clinical isolates as HR or non-HR to the often used β-lactam/inhibitor combination piperacillin-tazobactam using pre-screening and Population Analysis Profiling tests. We sequenced the isolates, assembled the whole genomes and created a set of predictors based on current knowledge of HR mechanisms. Then we trained several machine learning models on 80% of this data set aiming to detect HR isolates. We compared performance of the best ML models on the remaining 20% of the data set with a baseline model based solely on the presence of β-lactamase genes. Furthermore, we sequenced the resistant sub-populations in order to analyse the genetic mechanisms underlying HR.</p><p><strong>Findings: </strong>The best ML model achieved 100% sensitivity and 84.6% specificity, outperforming the baseline model. The strongest predictors of HR were the total number of β-lactamase genes, β-lactamase gene variants and presence of IS elements flanking them. Genetic analysis of HR strains confirmed that HR is caused by an increased copy number of resistance genes via gene amplification or plasmid copy number increase. This aligns with the ML model's findings, reinforcing the hypothesis that this mechanism underlies HR in Gram-negative bacteria.</p><p><strong>Interpretation: </strong>We demonstrate that a combination of WGS and ML can identify HR in bacteria with perfect sensitivity and high specificity. This improved detection would allow for better-informed treatment decisions and potentially reduce the occurrence of treatment failures associated with HR.</p><p><strong>Funding: </strong>Funding provided to DIA from the Swedish Research Council (2021-02091) and NIH (1U19AI158080-01).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"113 ","pages":"105618"},"PeriodicalIF":9.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476288","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":"The ongoing importance of patient-informed, collaborative research in advancing the definition and harmonization of post COVID-19 condition (PCC) subtypes across diverse populations.","authors":"Erin Collins, Nicole Shaver, Julian Little","doi":"10.1016/j.ebiom.2025.105592","DOIUrl":"10.1016/j.ebiom.2025.105592","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"113 ","pages":"105592"},"PeriodicalIF":9.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381881","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":"Linking epidemiology and genomics of maternal smoking during pregnancy in utero and in ageing: a population-based study using human foetuses and the UK Biobank cohort.","authors":"Mihail Mihov, Hannah Shoctor, Alex Douglas, David C Hay, Peter J O'Shaughnessy, John P Iredale, Sophie Shaw, Paul A Fowler, Felix Grassmann","doi":"10.1016/j.ebiom.2025.105590","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105590","url":null,"abstract":"<p><strong>Background: </strong>Maternal smoking and foetal exposure to nicotine and other harmful chemicals in utero remains a serious public health issue with little knowledge about the underlying genetics and consequences of maternal smoking in ageing individuals. Here, we investigated the epidemiology and genomic architecture of maternal smoking in a middle-aged population and compare the results to effects observed in the developing foetus.</p><p><strong>Methods: </strong>In the current project, we included 351,562 participants from the UK Biobank (UKB) and estimated exposure to maternal smoking status during pregnancy through self-reporting from the UKB participants about the mother's smoking status around their birth. In addition, we analysed 64 foetal liver transcriptomic expression datasets collected from women seeking elective pregnancy terminations. Foetal maternal smoking exposure was confirmed through measurement of foetal plasma cotinine levels.</p><p><strong>Findings: </strong>Foetal exposure to maternal smoking had a greater impact on males than females, with more differentially expressed genes in liver tissue (3313 vs. 1163) and higher liver pathway activation. In the UKB, maternal smoking exposure was linked to an unhealthy lifestyle, lower education, and liver damage. In a genome-wide analysis in the UKB, we leveraged the shared genetic basis between affected offspring and their mothers and identified five genome-wide significant regions. We found a low heritability of the trait (∼4%) and implicated several disease-related genes in a transcriptome-wide association study. Maternal smoking increased all-cause mortality risk (Hazard ratio and 95% CI: 1.10 [1.04; 1.16], P = 4.04 × 10^-4), which was attenuated in non-smoking males.</p><p><strong>Interpretation: </strong>Although male foetuses are more affected than females by maternal smoking in pregnancy, this effect was largely reduced in middle-aged individuals. Importantly, our results highlight that the overall 10% increased mortality due to maternal smoking in pregnancy was greatly attenuated in non-smokers. This study demonstrates the importance of campaigns promoting offspring smoking prevention in families where the parent(s) smoke.</p><p><strong>Funding: </strong>Funding for this project was provided by the University of Aberdeen, the Science Initiative Panel of the Institute of Medical Science, the UK Medical Research Council, the Seventh Framework Programme of the European Union under Grant Agreement 212885 (REEF) and by NHS Grampian Endowments grants.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"105590"},"PeriodicalIF":9.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of oral cannabis consumption during pregnancy on maternal spiral artery remodelling, fetal growth and offspring behaviour in mice.","authors":"Tyrah M Ritchie, Emily Feng, Fatemeh Vahedi, Sofya Ermolina, Christian J Bellissimo, Erica De Jong, Ana L Portillo, Sophie M Poznanski, Lauren Chan, Sara M Ettehadieh, Deborah M Sloboda, Dawn M E Bowdish, Ali A Ashkar","doi":"10.1016/j.ebiom.2025.105572","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105572","url":null,"abstract":"<p><strong>Background: </strong>The use of cannabis during pregnancy is rising following its widespread legalization. Cannabidiol (CBD) is gaining popularity due to the public perception that it is safer than the psychoactive cannabis component Δ9-tetrahydrocannabinol (THC). However, while evidence underpins the harm of THC and cannabis smoke on fetal development, there is minimal research on the safety of CBD and oral cannabis. The current study aims to decipher the safety of oral CBD and THC use during pregnancy.</p><p><strong>Methods: </strong>Using a mouse model, we directly compared the effects of oral CBD and THC oil exposure (20 mg/kg body weight) from early to mid-gestation on implantation site remodelling and fetal growth. We examined offspring behaviour and metabolic activity using both traditional and automated cage systems. Lastly, using human and mouse immune cells we assessed how CBD and THC influence angiogenic factor production.</p><p><strong>Findings: </strong>We observed impaired maternal spiral artery remodelling in cannabis exposed mice and found that CBD and THC disrupt immune cell angiogenic factor production. Oral consumption of THC or CBD oil also resulted in significant fetal growth impairment and led to long-lasting sex-dependent consequences as male offspring exhibited altered aggression and metabolic activity while females had impaired spatial learning.</p><p><strong>Interpretation: </strong>Our results show that oral consumption of either CBD or THC oil during pregnancy in mice results in harm to the developing fetus and causes behavioural changes after birth.</p><p><strong>Funding: </strong>The Michael G. DeGroote Centre for Medicinal Cancer Research, the Canadian Institutes of Health Research, and the Canadian Foundation for Innovation.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"105572"},"PeriodicalIF":9.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"homeRNA self-blood collection enables high-frequency temporal profiling of presymptomatic host immune kinetics to respiratory viral infection: a prospective cohort study.","authors":"Fang Yun Lim, Hannah G Lea, Ashley M Dostie, Soo-Young Kim, Tammi L van Neel, Grant W Hassan, Meg G Takezawa, Lea M Starita, Karen N Adams, Michael Boeckh, Joshua T Schiffer, Ollivier Hyrien, Alpana Waghmare, Erwin Berthier, Ashleigh B Theberge","doi":"10.1016/j.ebiom.2024.105531","DOIUrl":"10.1016/j.ebiom.2024.105531","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Early host immunity to acute respiratory infections (ARIs) is heterogenous, dynamic, and critical to an individual's infection outcome. Due to limitations in sampling frequency/timepoints, kinetics of early immune dynamics in natural human infections remain poorly understood. In this nationwide prospective cohort study, we leveraged a Tasso-SST based self-blood collection and stabilization tool (homeRNA) to profile detailed kinetics of the presymptomatic to convalescence host immunity to contemporaneous respiratory pathogens.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We enrolled non-symptomatic adults with recent exposure to ARIs who subsequently tested negative (exposed-uninfected) or positive for respiratory pathogens. Participants self-collected blood and nasal swabs daily for seven consecutive days followed by weekly blood collection for up to seven additional weeks. Symptom burden was assessed during each collection. Nasal swabs were tested for SARS-CoV-2 and common respiratory pathogens. 92 longitudinal blood samples spanning the presymptomatic to convalescence phase of eight participants with SARS-CoV-2 infection and 40 interval-matched samples from four exposed-uninfected participants were subjected to high-frequency longitudinal profiling of 785 immune genes. Generalized additive mixed models (GAMM) were used to identify temporally dynamic genes from the longitudinal samples and linear mixed models (LMM) were used to identify baseline differences between exposed-infected (n = 8), exposed-uninfected (n = 4), and uninfected (n = 13) participant groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between June 2021 and April 2022, 68 participants across 26 U.S. states completed the study and self-collected a total of 691 and 466 longitudinal blood and nasal swab samples along with 688 symptom surveys. SARS-CoV-2 was detected in 17 out of 22 individuals with study-confirmed respiratory infection, of which five were still presymptomatic or pre-shedding, enabling us to profile detailed expression kinetics of the earliest blood transcriptional response to contemporaneous variants of concern. 51% of the genes assessed were found to be temporally dynamic during COVID-19 infection. During the pre-shedding phase, a robust but transient response consisting of genes involved in cell migration, stress response, and T cell activation were observed. This is followed by a rapid induction of many interferon-stimulated genes (ISGs), concurrent to onset of viral shedding and increase in nasal viral load and symptom burden. Finally, elevated baseline expression of antimicrobial peptides was observed in exposed-uninfected individuals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;We demonstrated that unsupervised self-collection and stabilization of capillary blood can be applied to natural infection studies to characterize detailed early host immune kinetics at a temporal resolution comparable to that of human challenge studies. The remote (decentralized)","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"112 ","pages":"105531"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002162","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":"Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadth.","authors":"Katrina M Pollock, Hannah M Cheeseman, Leon R McFarlane, Suzanne Day, Monica Tolazzi, Hannah L Turner, Jennifer Joypooranachandran, Katsiaryna Shramko, Stefania Dispinseri, Philipp Mundsperger, Ilja Bontjer, Nana-Marie Lemm, Sofia Coelho, Maniola Tanaka, Tom Cole, Bette Korber, Dietmar Katinger, Quentin J Sattentau, Andrew B Ward, Gabriella Scarlatti, Rogier W Sanders, Robin J Shattock","doi":"10.1016/j.ebiom.2024.105544","DOIUrl":"10.1016/j.ebiom.2024.105544","url":null,"abstract":"<p><strong>Background: </strong>We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection.</p><p><strong>Methods: </strong>Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.2). All immunogens were co-formulated with liposomal Monophosphoryl-Lipid A (MPLA) adjuvant, and volunteers were followed up for 28 days post final Mosaic booster injection. Participants gave written informed consent to join the study. The study is registered on ClinicalTrials.gov ID NCT03816137.</p><p><strong>Findings: </strong>Fifty-one participants (men n = 23 and women n = 28) aged 18-55 were enrolled. The seroconversion rate against Env was 100% with all participants having measurable anti-Env IgG antibodies after their second injection and throughout the study. Neutralisation was detected against the ConM pseudovirus in sera of those who had received both ConM and ConS immunogens. However, this activity was limited in breadth and was neither boosted nor broadened in those receiving the Mos3.1 and Mos3.2 immunogens. Neutralising antibody function correlated with binding to V1/V3 and V5 epitopes and peaked after the third injection.</p><p><strong>Interpretation: </strong>Rationally designed prefusion-stabilised native-like Env trimers are robustly immunogenic in a prime-boost schedule. When given alone they are insufficient to induce neutralising antibody titres of significant breadth, but they represent potentially valuable polishing immunogens after germline-targeting.</p><p><strong>Funding: </strong>European Aids Vaccine initiative (EAVI2020) received funding from EU Horizon 2020, grant number 681137. Structural studies were supported by the Bill and Melinda Gates Foundation (INV-002916).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"112 ","pages":"105544"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926844","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":"Nanostructured lipid carriers based mRNA vaccine leads to a T cell-inflamed tumour microenvironment favourable for improving PD-1/PD-L1 blocking therapy and long-term immunity in a cold tumour model.","authors":"Carole Fournier, Marion Mercey-Ressejac, Valentin Derangère, Amal Al Kadi, David Rageot, Christine Charrat, Alexis Leroy, Julien Vollaire, Véronique Josserand, Marie Escudé, Séverine Escaich, François Ghiringhelli, Thomas Decaens, Fabrice P Navarro, Evelyne Jouvin-Marche, Patrice N Marche","doi":"10.1016/j.ebiom.2024.105543","DOIUrl":"10.1016/j.ebiom.2024.105543","url":null,"abstract":"<p><strong>Background: </strong>mRNA-based cancer vaccines show promise in triggering antitumour immune responses. To combine them with existing immunotherapies, the intratumoral immune microenvironment needs to be deeply characterised. Here, we test nanostructured lipid carriers (NLCs), the so-called Lipidots®, for delivering unmodified mRNA encoding Ovalbumin (OVA) antigen to elicit specific antitumour responses.</p><p><strong>Methods: </strong>We evaluated whether NLC OVA mRNA complexes activate dendritic cells (DCs) in vitro and identified the involved signalling pathways using specific inhibitors. We tested the anti-tumoral impact of Ova mRNA vaccine in B16-OVA and E.G7-OVA cold tumour-bearing C57Bl6 female mice as well as its synergy effect with an anti-PD-1 therapy by following the tumour growth and performing immunophenotyping of innate and adaptive immune cells. The intratumoral vaccine-related gene signature was assessed by RNA-sequencing. The immune memory response was assessed by re-challenging surviving treated mice with tumour cells.</p><p><strong>Findings: </strong>Our vaccine activates DCs in vitro through the TLR4/8 and ROS signalling pathways and induces specific T cell activation while exhibits significant preventive and therapeutic antitumour efficacy in vivo. A profound intratumoral remodelling of the innate and adaptive immunity in association with an increase in the gene expression of chemokines (Cxcl10, Cxcl11, Cxcl9) involved in CD8⁺ T cell attraction were observed in immunised mice. The combination of vaccine and anti-PD-1 therapy improves the rates of complete responses and memory immune responses compared to monotherapies.</p><p><strong>Interpretation: </strong>Lipidots® are effective platform for the development of vaccines against cancer based on mRNA delivery. Their combination with immune checkpoint blockers could counter tumour resistance and promote long-term antitumour immunity.</p><p><strong>Funding: </strong>This work was supported by Inserm Transfert, la Région Auvergne Rhône Alpes, FINOVI, and the French Ministry of Higher Education, research and innovation (LipiVAC, COROL project, funding reference N° 2102992411).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"112 ","pages":"105543"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964211","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":"Synapse vulnerability and resilience underlying Alzheimer's disease.","authors":"Raquel N Taddei, Karen E Duff","doi":"10.1016/j.ebiom.2025.105557","DOIUrl":"10.1016/j.ebiom.2025.105557","url":null,"abstract":"<p><p>Synapse preservation is key for healthy cognitive ageing, and synapse loss represents a critical anatomical basis of cognitive dysfunction in Alzheimer's disease (AD), predicting dementia onset, severity, and progression. Synapse loss is viewed as a primary pathologic event, preceding neuronal loss and brain atrophy in AD. Synapses may, therefore, represent one of the earliest and clinically most meaningful targets of the neuropathologic processes driving AD dementia. The synapse loss in AD is highly selective and targets particularly vulnerable synapses while leaving others, termed resilient, largely unaffected. Yet, the anatomic and molecular hallmarks of the vulnerable and resilient synapse populations and their association with AD neuropathologic changes (e.g. amyloid-β plaques and tau tangles) and memory dysfunction remain poorly understood. Characterising the selectively vulnerable and resilient synapses in AD may be key to understanding the mechanisms of cognitive preservation versus loss and enable the development of robust biomarkers and disease-modifying therapies for dementia.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"112 ","pages":"105557"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074170","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}