Biology of Sex Differences最新文献

{"title":"Sex-specific efficacy and safety of short-term and de-escalation DAPT strategies after PCI: a network meta-analysis.","authors":"Hao-Yun Lo, Su-Kiat Chua, Jen-Kuang Lee, Donna Shu-Han Lin","doi":"10.1186/s13293-026-00903-y","DOIUrl":"https://doi.org/10.1186/s13293-026-00903-y","url":null,"abstract":"<p><strong>Background: </strong>Sex differences in thrombotic and bleeding risks after percutaneous coronary intervention (PCI) are well established, yet it remains uncertain whether the efficacy and safety of modern dual antiplatelet therapy (DAPT) strategies differ between men and women.</p><p><strong>Objectives: </strong>This study aimed to compare sex-specific outcomes of contemporary short-term and de-escalation DAPT strategies to guide individualized post-PCI management.</p><p><strong>Methods: </strong>A network meta-analysis of randomized controlled trials reporting sex-stratified outcomes for alternative DAPT strategies versus standard DAPT was performed. Strategies were categorized as standard DAPT, guided de-escalation, short DAPT followed by aspirin or P2Y12 inhibitor (P2Y12i) monotherapy, de-escalation to clopidogrel, or de-escalation to reduced-dose P2Y12i. The primary outcomes were major adverse cardiovascular events (MACE), bleeding, and net adverse clinical events (NACE).</p><p><strong>Results: </strong>A total of 25 trials including 115,223 men and 38,574 women were analyzed. For MACE, no strategy was superior in men, while de-escalation to clopidogrel showed a favorable trend in women. In men, short DAPT followed by aspirin (risk ratio [RR] 0.44, 95% confidence interval [CI] 0.27-0.73) or P2Y12 inhibitor monotherapy (RR 0.52, 95% CI 0.39-0.70) reduced bleeding, whereas this benefit was not observed in women (P for sex difference = 0.015). De-escalation to clopidogrel provided the lowest bleeding risk and the most favorable NACE profile in women.</p><p><strong>Conclusions: </strong>Sex-based differences exist in the optimal DAPT strategy following PCI, with short DAPT followed by monotherapy robustly reducing bleeding risk in men, while de-escalation to clopidogrel showed the most favorable profile for bleeding and net clinical outcomes in women. However, this finding should be considered hypothesis-generating pending confirmatory evidence, and underscores the need for dedicated prospective trials evaluating sex-specific antiplatelet strategies after PCI.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in proteomic response to ischemic stroke.","authors":"Christopher J McLouth, Hunter S Hazelwood, Jacqueline A Frank, Jordan P Harp, David Dornbos, Justin F Fraser, Keith R Pennypacker","doi":"10.1186/s13293-026-00907-8","DOIUrl":"https://doi.org/10.1186/s13293-026-00907-8","url":null,"abstract":"<p><strong>Background: </strong>Women often experience greater disability after ischemic stroke than men, but the biological mechanisms underlying these differences remain unclear. Proteomic analysis may identify sex-specific molecular pathways that contribute to stroke rehabilitation and recovery.</p><p><strong>Methods: </strong>We analyzed plasma samples from 141 patients enrolled in the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC). Expression of 184 inflammatory and cardiometabolic proteins, measured proximal and distal to the clot, was quantified using Olink panels. Associations between protein expression and discharge outcomes - including the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS), and Montreal Cognitive Assessment (MoCA) - were evaluated with models including a sex by protein interaction term, adjusting for clinical and demographic covariates.</p><p><strong>Results: </strong>The median age was 69 years, and 55% were women. After controlling the false discovery rate, systemic TGFBI was expressed at higher levels in men. Multiple proteins demonstrated sex-specific associations with discharge outcomes. For NIHSS, systemic PCOLCE and NT3, as well as intracranial FGF5, NT3, TNFSF14, and TWEAK, were differentially associated by sex, with higher expression generally linked to worse outcomes in women and protective trends in men. For mRS, systemic ICAM3 and TGFBI were associated with higher odds of poor mRS scores in women, while SELL showed a potential protective effect in men. Intracranial CD6 and LAP TGF-β1 also demonstrated sex-specific associations with mRS scores. No sex-specific associations were observed for MoCA.</p><p><strong>Conclusions: </strong>Several sex dependent proteins were associated with post-stroke discharge outcomes. These findings suggest that sex-specific molecular responses could contribute to disparities in post-stroke recovery and highlight the importance of incorporating sex as a biological variable in biomarker studies as well as stratifying clinical trials based on sex.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 APOE genotype, age, and sex on gut microbiota in a mouse model of Alzheimer's Disease: an exploration of their interactions.","authors":"Xue Mi, Yi-Chi Zhang, Xu-Jun Zhang, Hao-Bing He, Xiao-Chun Chen, Xiao-Man Dai","doi":"10.1186/s13293-026-00905-w","DOIUrl":"https://doi.org/10.1186/s13293-026-00905-w","url":null,"abstract":"<p><strong>Background: </strong>As an important interface between the peripheral environment and the central nervous system, the gut microbiota varies greatly between patients or animals with Alzheimer's disease (AD) and their respective non-AD counterparts; however, it remains unexplored whether the apolipoprotein E (APOE) genotype, age, and sex may interactively influence the characteristics of gut microbiota in AD animals.</p><p><strong>Methods: </strong>APOE genotype, age, and sex were enrolled as independent variables, with genotype distinguished into APOE3 and APOE4, age into 3 and 10 months, and sex into female and male. The composition, structure, and potential functions of gut microbiota were systematically analyzed by 16S rRNA gene amplicon sequencing to evaluate the individual and interactive effects of APOE genotype, age and sex.</p><p><strong>Results: </strong>Significant interactions were observed among APOE genotypes, ages, and sexes, with different factor combinations exhibiting distinct effect on microbiotic composition and functional potential. APOE genotype exerted the most significant influence on gut microbiota, followed by age and sex with a relatively minor effect, highlighting the dominant role of host genetic background. Functional prediction analysis indicated that the functional profiles were mainly concentrated in basic metabolic pathways, including the biosynthesis of secondary metabolites and amino acids, and carbon metabolism.</p><p><strong>Conclusion: </strong>APOE genotype, age, and sex are jointly associated with the structure and potential function of the gut microbiota in AD model mice. These findings provide a perspective of multi-factor interaction into the alterations in gut microbiota in AD and offer new microecological evidence for understanding APOE4-related AD susceptibility, as well as a conceptual basis for future stratified microecological intervention studies.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex influences on tumor innervation.","authors":"Sarah M Barclay, Jeffrey Barr, Oduduabasi Isaiah, Mangalam Bajpai, Hailey Bullard, Ethan Neufeld, Craig C Welbon, Payal Ghosh, Destiny S Brockhaus, William C Spanos, Paola D Vermeer","doi":"10.1186/s13293-026-00887-9","DOIUrl":"10.1186/s13293-026-00887-9","url":null,"abstract":"<p><p>Peripheral solid malignancies are infiltrated by nerves. Using syngeneic cell lines, we set out to define whether sex influences tumor innervation in oral cancers and melanoma. Tumors grew significantly slower in females and were significantly more innervated than in males. In oral cancer, tumor-infiltrating nerves connect to a pre-existing neural circuit that enters the brain and impacts behavior. Thus, we evaluated the impact of sex on this circuit and assessed the behavioral consequences. We found no differences in the timing or extent of behavioral declines between oral tumor-bearing males and females. Moreover, in untreated mice, metastasis did not differ by sex. Treatment of oral tumors with cisplatin and radiation slowed tumor growth in male and female mice but significantly increased tumor innervation with females harboring the greatest innervation density. Treated females also harbored significantly increased metastases in their lungs compared to treated males. Treatment improved tumor-associated behavioral changes. While the tumor-brain circuit did not differ between males and females, the activation status of neurons and glia in projection areas significantly increased on the ipsilateral side. This heightened activation was attenuated following cisplatin/radiation treatment. These studies indicate that peripheral malignancies activate neurons and glia in central nervous system (CNS) projection areas, and that standard-of-care therapy attenuates this, which correlates with improved behavior. These findings emphasize that sex influences peripheral tumor-infiltrating nerves and brain function (via the tumor-brain circuit) and suggest that severing or silencing this circuit could improve patient outcomes.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex- and age-dependent mitochondrial dysfunction and cognitive impairment in a mouse model of familial hypercholesterolemia.","authors":"Nathasha Prado-Lopes, Daniel Fagundes, Letícia Tavares, Whitney Santos, Wellinghton Barros, Henrique Moschen, Márcia Mortari, Jair Goulart, Angélica Amato, Jade de Oliveira, Paula Bellozi, Andreza Fabro de Bem","doi":"10.1186/s13293-026-00893-x","DOIUrl":"https://doi.org/10.1186/s13293-026-00893-x","url":null,"abstract":"<p><strong>Background: </strong>Familial hypercholesterolemia (FH) is a genetic disorder of cholesterol metabolism caused by loss-of-function variants in the low-density lipoprotein receptor (LDLR), resulting in persistently elevated LDL-cholesterol levels in plasma. Although hypercholesterolemia, especially the high levels of LDL, has been linked to an increased risk of dementia, the underlying mechanisms remain unclear. Here, we investigated the effects of sexual dimorphism and aging on metabolic and cognitive functions in a murine model of FH.</p><p><strong>Methods: </strong>Adult and middle-aged, male and female, C57BL/6 and LDLr^-/- mice were used in this study. Behavioral assessments included locomotor activity, spatial memory, and anxiety-like behavior. Plasma lipid profiles were measured, and mitochondrial function in the hippocampus and brown adipose tissue (BAT) was assessed using high-resolution respirometry.</p><p><strong>Results: </strong>LDLr^-/- mice of both sexes exhibited increased cholesterol and triglycerides levels. Male LDLr^-/- mice displayed hyperlocomotion in the Open Field (OF) and Elevated Plus Maze (EPM) at both ages, whereas this phenotype emerged in middle-aged female LDLr^-/- mice only in OF. Spatial memory impairments were observed in LDLr^-/- mice regardless of sex or age. Hippocampal oxygen consumption was reduced in adult males and middle-aged female mice, whereas BAT respiration was impaired in both sexes at middle-aged animals, affecting distinct respiratory parameters. Correlation analyses revealed that elevated cholesterol levels were associated with memory deficits and hyperlocomotion, along with positive correlations between hippocampal and BAT mitochondrial function.</p><p><strong>Conclusions: </strong>Collectively, these findings demonstrate that FH induces sex- and age-dependent alterations in behavior and mitochondrial metabolism, providing mechanistic insights into the link between FH and neurodegenerative disease risk.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A transient sex-biased transcriptional program shapes early postnatal L2/3 neuron development.","authors":"Elia Marcos-Grañeda, Fernando Martín-Fernández, Linnea A Weiss, Juan C Oliveros, Marta Nieto","doi":"10.1186/s13293-026-00885-x","DOIUrl":"https://doi.org/10.1186/s13293-026-00885-x","url":null,"abstract":"<p><p>Most neurodevelopmental disorders (NDDs), including intellectual disability, epilepsy, and autism spectrum disorder (ASD), exhibit marked sex differences in risk, incidence, prognosis, and clinical presentation. Increasing evidence suggests that these disorders often originate from alterations in circuit formation that occur during critical developmental windows preceding the onset of symptoms. However, the extent to which sexual dimorphism emerges during neuronal differentiation remains largely underexplored in the context of NDD research. In the cerebral cortex, layer (L) 2/3 excitatory pyramidal neurons, which integrate information across cortical areas and hemispheres, have been broadly implicated in NDDs. In this study, we investigate the transcriptional expression dynamics of L2/3 neurons across three developmental stages-embryonic day (E) 19, postnatal day (P) 4, and P7-and identify a window of transient, sex-biased gene expression at P4, possibly related to the process of brain masculinization. Furthermore, gene expression analysis following knockout (KO) mutations of Cux1 and Cux2 in L2/3 neurons reveals sex-biased dysregulation, with male neurons exhibiting heightened susceptibility and amplified transcriptional disruption, resulting in a molecular fingerprint that is distinct from their WT counterparts. These findings underscore the need to incorporate studies of sex-dependent differentiation trajectories as a biological variable in NDD research and may inform the development of more targeted, sex-specific therapeutic strategies.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical thickness, surface area, and multisite pain: distinct patterns by sex in adolescence.","authors":"Esmeralda Hidalgo-Lopez, Christel Portengen, Tristin Smith, Hannah C Becker, Andrew Schrepf, Steven E Harte, Adriene M Beltz, Chelsea M Kaplan","doi":"10.1186/s13293-026-00898-6","DOIUrl":"https://doi.org/10.1186/s13293-026-00898-6","url":null,"abstract":"<p><strong>Background: </strong>Multisite pain is common during adolescence and is influenced by sex-related neurobiological and developmental factors, but its developmental neural mechanisms are unclear.</p><p><strong>Methods: </strong>Utilizing data from the Adolescent Brain and Cognitive Development Study, we investigated the relation between cortical brain structure and multisite pain (assessed by youth self-reports of painful regions on a body map) in male (N = 3,299) and female (N = 2,844) adolescents aged 11-12 years. We focused on brain regions functionally linked to multisite pain (i.e., bilateral sensorimotor, cingulate, fronto-insular and inferior parietal cortex). We also explored the moderating role of pubertal status (assessed by the Pubertal Development Scale).</p><p><strong>Results: </strong>Findings revealed distinct brain structure-pain associations in male and female youth. Male youth exhibited an inverse linear relation between cortical thickness of the left pre- and postcentral gyri and number of pain sites. Female youth exhibited a non-linear relation between surface area of the right supramarginal gyrus and number of pain sites. Pubertal status moderated the cingulate cortical thickness-pain association in males; those in early puberty had an inverse relation between anterior and mid cingulate cortex thickness and pain sites, whereas this relation was positive in those beyond mid-puberty.</p><p><strong>Conclusion: </strong>This study provides valuable insights into the sex-dependent neural organization linked to adolescent pain.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex shapes CD64 expression and vaccine-induced monocytic responses.","authors":"Charlotte Sophie Hansen, Julie Sellau, Anastasia Langanz, Leonie Marie Weskamm, Nele Wichern, Annika Bea, Johannes Brandi, Helena Fehling, Nils Groth, Melanie Lütkemeyer, Matthias Knödler, Henrik Nausch, Eirini Stivachti, Barbara Honecker, Hanna Lotter","doi":"10.1186/s13293-026-00897-7","DOIUrl":"10.1186/s13293-026-00897-7","url":null,"abstract":"<p><p>Sex-specific differences influence vaccine-induced immunity, with females generally mounting more robust immune responses than males. While enhanced antibody production in females is well established, the cellular mechanisms underlying these differences remain elusive. Monocytes and monocyte-derived dendritic cells contribute to vaccine-induced immunity by capturing antibody-antigen immune complexes via Fc gamma receptors (FcγRs), positioning them as potential mediators of sex-biased vaccine responses. Here, we investigated sex-specific differences in FcγRI (CD64)-expressing monocytic cells in humans and mice. Using flow cytometry, we demonstrate that healthy women display higher frequencies of CD64-positive monocytes and elevated CD64 expression in peripheral blood compared with men. In mice, a similar sex-specific pattern was consistently reproduced across diverse experimental settings, including in vitro and in vivo conditions. Functional in vitro assays revealed that classical monocytes from female mice mediated stronger classical antigen presentation to CD4⁺ T cells than male-derived monocytes in a CD64-dependent manner, as reflected by increased IFNγ production. In parallel, female-derived monocytes also displayed enhanced cross-presentation to CD8⁺ T cells; however, this effect occurred independently of CD64. Following intramuscular vaccination, flow cytometric analysis demonstrated that female mice exhibited increased frequencies of CD64-positive monocytes at the injection site, accompanied by higher CD64 surface expression levels on these cells. In addition, females showed significantly greater accumulation of monocytic cells in dorsal lymph nodes compared with males. Notably, castration of male mice enhanced monocytic recruitment to muscle tissue following immunization, indicating a role for sex hormones in regulating monocytic responses to vaccination. Together, these findings identify sex-specific regulation of CD64⁺ monocytic cells as a mechanism associated with enhanced antigen presentation in females and suggest that this pathway contributes to stronger vaccine-induced immune responses. In this context, our data underscore the relevance of biological sex in shaping Fcγ receptor-mediated immune mechanisms relevant to vaccination.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13081479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in dynamic and static measures of brain integration derived from resting-state functional magnetic resonance imaging.","authors":"Xiaojing Fang, Olivia Schwemmer, Abigail Hogan, Michael Marxen","doi":"10.1186/s13293-026-00891-z","DOIUrl":"10.1186/s13293-026-00891-z","url":null,"abstract":"<p><strong>Background: </strong>Understanding the impact of biological sex on the functional organization and dynamics of the brain is crucial for elucidating sex-specific differences in cognitive functions and neuropsychiatric disorders. Systems neuroscience often models the brain as a network of interconnected brain regions with functional connectivity (FC), i.e., the correlation between signal time courses, serving as a measure of connection strength. FC matrices, here derived from resting-state functional magnetic resonance imaging (rs-fMRI), define a network graph that can be characterized by its level of module segregation or, inversely, integration. Such parameters can be generated for the full length of the acquired data (static) or for short periods implying dynamically changing brain states. We recently made the interesting observation in a separate study (N = 63) that measures of brain integration and segregation based on dynamic functional connectivity (dFC) data differed between sexes, while graph-based measures based on static FC (sFC) did not, which we investigated in more detail in this study.</p><p><strong>Methods: </strong>We preregistered a replication of our analysis from the small sample in N = 501 subjects of the Human Connectome Project dataset. We performed cross-sectional comparisons between sexes of the static rs-fMRI graph parameters modularity and global efficiency, as well as the dFC parameters state prevalence, mean dwell time, mean inter-state transition time, and variability derived from a two-state model. Additionally, we explored whether sex differences in 66 cognitive and behavioral parameters are mediated by the FC integration measure with the strongest sex effect.</p><p><strong>Results: </strong>All static and dynamic measures of integration/segregation showed higher levels of functional integration in males, with effect sizes up to 0.60 for the dFC parameter prevalence. For three of the 66 explored cognitive and behavioral parameters, we observed that the prevalence of the integrated state mediated the sex difference: dexterity, agreeableness, and self-reported aggression.</p><p><strong>Conclusion: </strong>We found consistent evidence across two datasets that rs-fMRI-based measures of brain integration are increased in males. An exploratory analysis, which requires replication, suggests that such differences mediate personality differences. This study highlights that biological sex differences in brain functional organization may contribute to sex-typical behaviors.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences for clinical presentations and co-pathologies in four-repeat tauopathies.","authors":"Ece Bayram, Danelle J Carter, Sana Aslam, Emily Forbes, Samantha K Holden","doi":"10.1186/s13293-026-00899-5","DOIUrl":"https://doi.org/10.1186/s13293-026-00899-5","url":null,"abstract":"<p><strong>Background: </strong>Four-repeat (4R)-tauopathies cause variable clinical profiles leading to clinical misdiagnosis. While sex differences are reported in Alzheimer's disease (AD), Lewy body disease (LBD), and clinically-defined frontotemporal dementia (FTD), little is known in 4R-tauopathies.</p><p><strong>Methods: </strong>National Alzheimer's Coordinating Center data were used for pathologically-defined 4R-tauopathies: progressive supranuclear palsy (PSP, n = 175), corticobasal degeneration (CBD, n = 114), argyrophilic grain disease (AGD, n = 230), Other-4R (n = 67). Sex differences for clinical presentation and co-pathologies were assessed adjusting for age and multiple comparisons.</p><p><strong>Results: </strong>Most common clinical diagnosis was PSP (41%) for PSP; unspecified FTD (36%) for CBD; AD for AGD (57%) and Other-4R groups (48%), without sex differences. Females had less cognitive decline, apathy, motor symptoms; were older at cognitive, behavioral change onset. Males were more likely to demonstrate LBD co-pathology and clinical profile.</p><p><strong>Conclusion: </strong>Both females and males have low clinical diagnostic accuracy for 4R-tauopathies. Females with 4R-tauopathies may experience less severe clinical presentations and less co-pathology.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}