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The characteristics of severe human parainfluenza virus (HPIV)-associated pneumonia in adults have not been well evaluated. We investigated epidemiologic and clinical characteristics of 143 patients with severe HPIV-associated pneumonia during 2010-2019. HPIV was the most common cause (25.2%) of severe virus-associated hospital-acquired pneumonia and the third most common cause (15.7%) of severe virus-associated community-acquired pneumonia. Hematologic malignancy (35.0%), diabetes mellitus (23.8%), and structural lung disease (21.0%) were common underlying conditions. Co-infections occurred in 54.5% of patients admitted to an intensive care unit. The 90-day mortality rate for HPIV-associated pneumonia was comparable to that for severe influenza virus-associated pneumonia (55.2% vs. 48.4%; p = 0.22). Ribavirin treatment was not associated with lower mortality rates. Fungal co-infections were associated with 82.4% of deaths. Clinicians should consider the possibility of pathogenic co-infections in patients with HPIV-associated pneumonia. Contact precautions and environmental cleaning are crucial to prevent HPIV transmission in hospital settings.
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Infecções Comunitárias Adquiridas , Centros de Atenção Terciária , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/virologia , República da Coreia/epidemiologia , Idoso , Adulto , Pneumonia Associada a Assistência à Saúde/epidemiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Coinfecção/epidemiologia , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/mortalidade , História do Século XXI , Infecção Hospitalar/epidemiologia , Adulto Jovem , Idoso de 80 Anos ou maisRESUMO
PURPOSE: Distinguishing between complicated and uncomplicated Staphylococcus aureus bacteraemia (SAB) is therapeutically essential. However, this distinction has limitations in reflecting the heterogeneity of SAB and encouraging targeted diagnostics. Recently, a new risk stratification system for SAB metastatic infection, involving stepwise approaches to diagnosis and treatment, has been suggested. We assessed its applicability in methicillin-resistant SAB (MRSAB) patients. METHODS: We retrospectively analysed data of a 3-year multicentre, prospective cohort of hospitalised patients with MRSAB. We classified the patients into three risk groups: low, indeterminate, and high, based on the new system and compared between-group management and outcomes. RESULTS: Of 380 patients with MRSAB, 6.3% were classified as low-, 7.6% as indeterminate-, and 86.1% as high-risk for metastatic infection. No metastatic infection occurred in the low-, 6.9% in the indeterminate-, and 19.6% in the high-risk groups (P < 0.001). After an in-depth diagnostic work-up, patients were finally diagnosed as 'without metastatic infection (6.3%)', 'with metastatic infection (17.4%)', and 'uncertain for metastatic infection (76.3%)'. 30-day mortality increased as the severity of diagnosis shifted from 'without metastatic infection' to 'uncertain for metastatic infection' and 'with metastatic infection' (P = 0.09). In multivariable analysis, independent factors associated with metastatic complications were suspicion of endocarditis in transthoracic echocardiography, clinical signs of metastatic infection, Pitt bacteraemia score ≥ 4, and persistent bacteraemia. CONCLUSIONS: The new risk stratification system shows promise in predicting metastatic complications and guiding work-up and management of MRSAB. However, reducing the number of cases labelled as 'high-risk' and 'uncertain for metastatic infection' remains an area for improvement.
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Bacteriemia , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/diagnóstico , Bacteriemia/mortalidade , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Idoso de 80 Anos ou mais , Adulto , Fatores de RiscoRESUMO
Although research on aspergillosis and mucormycosis confection is important to optimize antifungal therapy, data on this issue is scarce. Thus, we systematically investigated aspergillosis coinfection in patients with proven mucormycosis. Medical records of adult patients with proven mucormycosis whose formalin-fixed paraffin-embedded (FFPE) tissue sections were available, in a tertiary hospital from August 2007 to July 2023 were retrospectively reviewed to assess coinfection with aspergillosis. We noted cultures of fungi from sterile and non-sterile sites and performed PCR assays on FFPE tissues to detect Aspergillus- and Mucorales-specific DNA. Sixty-seven patients with proven mucormycosis, including 12 (18%) with positive culture of the mucormycosis agent from sterile site cultures, were enrolled. Fungal cultures from sterile and non-sterile sites revealed Aspergillus spp. growth in 9 (13%) of the 67 patients, including 2 sterile and 7 non-sterile cultures. The fungal PCR analysis from the FFPE sections was positive for Aspergillus-specific PCR in 5 (7%) and positive for both Aspergillus- and Mucorales-specific PCR results in 8 (12%). Overall, 21 (31%) of the 67 patients with proven mucormycosis had microbiologic and/or molecular evidence of aspergillosis coinfection. Positive blood or bronchoalveolar lavage fluid galactomannan results were more common in the coinfection group (67% [14/21]) than in the mucormycosis group (37% [17/46], P = 0.024). No significant difference in mortality between the two groups was observed. Approximately one-third of patients with proven mucormycosis exhibited molecular and/or microbiologic evidence of aspergillosis coinfection. Further research is needed to identify patients with aspergillosis and mucormycosis coinfections, for optimal antifungal therapy.
The study aims to investigate the coinfection between mucormycosis and aspergillosis. Key findings reveal that approximately 31% of patients demonstrated evidence of coinfection, which emphasizes the importance of considering both pathogens in diagnosis and treatment decisions.
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BACKGROUND: Pulmonary nocardiosis is a rare opportunistic infection with occasional systemic dissemination. This study aimed to investigate the computed tomography (CT) findings and prognosis of pulmonary nocardiosis associated with dissemination. METHODS: We conducted a retrospective analysis of patients diagnosed with pulmonary nocardiosis between March 2001 and September 2023. We reviewed the chest CT findings and categorized them based on the dominant CT findings as consolidation, nodules and/or masses, consolidation with multiple nodules, and nodular bronchiectasis. We compared chest CT findings between localized and disseminated pulmonary nocardiosis and identified significant prognostic factors associated with 12-month mortality using multivariate Cox regression analysis. RESULTS: Pulmonary nocardiosis was diagnosed in 75 patients, of whom 14 (18.7%) had dissemination, including involvement of the brain in 9 (64.3%) cases, soft tissue in 3 (21.4%) cases and positive blood cultures in 3 (21.4%) cases. Disseminated pulmonary nocardiosis showed a higher frequency of cavitation (64.3% vs. 32.8%, P = 0.029) and pleural effusion (64.3% vs. 29.5%, P = 0.014) compared to localized infection. The 12-month mortality rate was 25.3%. The presence of dissemination was not a significant prognostic factor (hazard ratio [HR], 0.80; confidence interval [CI], 0.23-2.75; P = 0.724). Malignancy (HR, 9.73; CI, 2.32-40.72; P = 0.002), use of steroid medication (HR, 3.72; CI, 1.33-10.38; P = 0.012), and a CT pattern of consolidation with multiple nodules (HR, 4.99; CI, 1.41-17.70; P = 0.013) were associated with higher mortality rates. CONCLUSION: Pulmonary nocardiosis with dissemination showed more frequent cavitation and pleural effusion compared to cases without dissemination, but dissemination alone did not affect the mortality rate of pulmonary nocardiosis.
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Pneumopatias , Nocardiose , Derrame Pleural , Adulto , Humanos , Pneumopatias/diagnóstico por imagem , Pneumopatias/tratamento farmacológico , Nocardiose/diagnóstico , Nocardiose/tratamento farmacológico , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Our study analyzed 95 solid organ transplant (SOT) and 78 hematopoietic stem cell transplant (HSCT) recipients with prior coronavirus disease 2019 (COVID-19). Patients who underwent transplantation within 30 days of COVID-19 infection comprised the early group, and those who underwent transplantation post-30 days of COVID-19 infection comprised the delayed group. In the early transplantation group, no patient, whether undergoing SOT and HSCT, experienced COVID-19-associated complications. In the delayed transplantation group, one patient each from SOT and HSCT experienced COVID-19-associated complications. Additionally, among early SOT and HSCT recipients, two and six patients underwent transplantation within seven days of COVID-19 diagnosis, respectively. However, no significant differences were observed in the clinical outcomes of these patients compared to those in other patients. Early transplantation following severe acute respiratory syndrome coronavirus 2 infection can be performed without increased risk of COVID-19-associated complications. Therefore, transplantation needs not be delayed by COVID-19 infection.
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COVID-19 , Transplante de Órgãos , Humanos , Teste para COVID-19 , SARS-CoV-2 , TransplantadosRESUMO
INTRODUCTION: Fundamental questions remain about the key mechanisms that initiate Alzheimer's disease (AD) and the factors that promote its progression. Here we report the successful generation of the first genetically engineered marmosets that carry knock-in (KI) point mutations in the presenilin 1 (PSEN1) gene that can be studied from birth throughout lifespan. METHODS: CRISPR/Cas9 was used to generate marmosets with C410Y or A426P point mutations in PSEN1. Founders and their germline offspring are comprehensively studied longitudinally using non-invasive measures including behavior, biomarkers, neuroimaging, and multiomics signatures. RESULTS: Prior to adulthood, increases in plasma amyloid beta were observed in PSEN1 mutation carriers relative to non-carriers. Analysis of brain revealed alterations in several enzyme-substrate interactions within the gamma secretase complex prior to adulthood. DISCUSSION: Marmosets carrying KI point mutations in PSEN1 provide the opportunity to study the earliest primate-specific mechanisms that contribute to the molecular and cellular root causes of AD onset and progression. HIGHLIGHTS: We report the successful generation of genetically engineered marmosets harboring knock-in point mutations in the PSEN1 gene. PSEN1 marmosets and their germline offspring recapitulate the early emergence of AD-related biomarkers. Studies as early in life as possible in PSEN1 marmosets will enable the identification of primate-specific mechanisms that drive disease progression.
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Doença de Alzheimer , Callithrix , Presenilina-1 , Animais , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Animais Geneticamente Modificados , Encéfalo/patologia , Encéfalo/metabolismo , Sistemas CRISPR-Cas , Modelos Animais de Doenças , Técnicas de Introdução de Genes , Mutação/genética , Mutação Puntual/genética , Presenilina-1/genéticaRESUMO
Respiratory syncytial virus (RSV) constitutes a significant cause of respiratory illness and mortality among older adults, a demographic that is expanding with considerable impact on healthcare systems worldwide. The actual burden of RSV in this population may still be underestimated, owing to factors such as low awareness and suboptimal diagnostic sensitivity in adults, the lack of robust RSV surveillance systems, and the infrequent use of diagnostic testing. Recent advancements in respiratory virus detection have spurred further exploration into appropriate preventive and therapeutic strategies. The recent approval of two vaccines highlights the critical need for the precise estimation of the RSV disease burden to optimize the effectiveness and cost-efficiency of immunization programs. This narrative review aimed to summarize the existing knowledge of the RSV burden in adults with a particular focus on older adults, incorporating data from Korea. Overall, current estimates indicate that the annual RSV attack rate in the general adult population ranges from 1 - 7%, increasing to approximately 4 - 10% among elderly and high-risk groups. The in-hospital mortality rate can be estimated to be around 7 - 10%, rising up to 40% among intensive care unit-admitted patients. To elucidate RSV's disease burden, further continuing research, including population-based studies, is necessary.
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We establish a reliable method for selectively delivering adeno-associated viral vectors (AAVs) across the blood-brain barrier (BBB) in the marmoset without the need for neurosurgical injection. We focally perturbed the BBB (â¼1 × 2 mm) in area 8aD of the frontal cortex in four adult marmoset monkeys using low-intensity transcranial focused ultrasound aided by microbubbles. Within an hour of opening the BBB, either AAV2 or AAV9 was delivered systemically via tail-vein injection. In all four marmosets, fluorescence-encoded neurons were observed at the site of BBB perturbation, with AAV2 showing a sparse distribution of transduced neurons when compared to AAV9. The results are compared to direct intracortical injections of anterograde tracers into area 8aD and similar (albeit sparser) long-range connectivity was observed. With evidence of transduced neurons specific to the region of BBB opening as well as long-distance tracing, we establish a framework for focal noninvasive transgene delivery to the marmoset brain.
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Encéfalo , Callithrix , Animais , Encéfalo/fisiologia , Barreira Hematoencefálica , Transgenes , NeurôniosRESUMO
The production of endogenous hydrogen sulfide (H2S) is an important phenotype of bacteria. H2S plays an important role in bacterial resistance to ROS and antibiotics, which significantly contributes to bacterial pathogenicity. Edwardsiella piscicida, the Gram-negative pathogen causing fish edwardsiellosis, has been documented to produce hydrogen sulfide. In the study, we revealed that Ferric uptake regulator (Fur) controlled H2S synthesis by activating the expression of phsABC operon. Besides, Fur participated in the bacterial defense against ROS and cationic antimicrobial peptides and modulated T3SS expression. Furthermore, the disruption of fur exhibited a significant in vivo colonization defect. Collectively, our study demonstrated the regulation of Fur in H2S synthesis, stress response, and virulence, providing a new perspective for better understanding the pathogenesis of Edwardsiella.
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Proteínas de Bactérias , Edwardsiella , Infecções por Enterobacteriaceae , Doenças dos Peixes , Regulação Bacteriana da Expressão Gênica , Sulfeto de Hidrogênio , Estresse Fisiológico , Edwardsiella/genética , Edwardsiella/patogenicidade , Sulfeto de Hidrogênio/metabolismo , Animais , Virulência , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Infecções por Enterobacteriaceae/microbiologia , Doenças dos Peixes/microbiologia , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Espécies Reativas de Oxigênio/metabolismo , Óperon , Peptídeos Catiônicos Antimicrobianos/farmacologia , Sistemas de Secreção Tipo III/metabolismo , Sistemas de Secreção Tipo III/genética , Peixe-Zebra/microbiologiaRESUMO
We evaluated the clinical performance of the T2Candida assay. The overall agreement of the T2Candida assay results with the blood culture results was 95.3 % (121/127). The T2Candida assay detected three Candida albicans/tropicalis-positive specimens and one Candida krusei/glabrata-positive specimen; however, it did not detect two Candida glabrata specimens.
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Candida , Candidemia , Humanos , Candidemia/diagnóstico , Candidemia/microbiologia , Candida/isolamento & purificação , Candida/classificação , Sensibilidade e Especificidade , Hemocultura/métodosRESUMO
Modulation of cell death is a powerful strategy employed by pathogenic bacteria to evade host immune clearance and occupy profitable replication niches during infection. Intracellular pathogens employ the type III secretion system (T3SS) to deliver effectors, which interfere with regulated cell death pathways to evade immune defenses. Here, we reveal that poly(ADP-ribose) polymerase-1 (PARP1)-dependent cell death restrains Edwardsiella piscicida's proliferation in mouse monocyte macrophages J774A.1, of which PARP1 activation results in the accumulation of poly(ADP-ribose) (PAR) and enhanced inflammatory response. Moreover, E. piscicida, an important intracellular pathogen, leverages a T3SS effector YfiD to impair PARP1's activity and inhibit PAR accumulation. Once translocated into the host nucleus, YfiD binds to the ADP-ribosyl transferase (ART) domain of PARP1 to suppress its PARylation ability as the pharmacological inhibitor of PARP1 behaves. Furthermore, the interaction between YfiD and ART mainly relies on the complete unfolding of the helical domain, which releases the inhibitory effect on ART. In addition, YfiD impairs the inflammatory response and cell death in macrophages and promotes in vivo colonization and virulence of E. piscicida. Collectively, our results establish the functional mechanism of YfiD as a potential PARP1 inhibitor and provide more insights into host defense against bacterial infection.
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Edwardsiella , Infecções por Enterobacteriaceae , Animais , Camundongos , Sistemas de Secreção Tipo III/metabolismo , Poli Adenosina Difosfato Ribose , Virulência , Edwardsiella/metabolismoRESUMO
Pistacia chinensis and Pistacia weinmannifolia are small trees and are distributed in East Asia, in particular China. The data on P. chinensis presented in this article is associated with the research article, "DOI: 10.5010/JPB.2019.46.4.274" [1]. Both P. chinensis and P. weinmannifolia have long been used as ethnobotanical plants to treat various illnesses, including dysentery, inflammatory swelling, rheumatism, liver diseases, influenza, lung cancer, etc. Many studies have been carried out to delve into the pharmaceutical properties of these Pistacia species using plant extracts, but genomic studies are very rarely performed to date. To enrich the genetic information of these two species, RNA sequencing was conducted using a pair-end Illumina HiSeq2500 sequencing system, resulting in 2.6 G of raw data from P. chinensis (Accession no: SRR10136265) and 2.7 G bases from P. weinmannifolia (Accession no: SRR10136264). Transcriptome shotgun assembly using three different assembly tools generated a total of 18,524 non-redundant contigs (N50, 1104 bp) from P. chinensis and 18,956 from P. weinmannifolia (N50, 1137 bp). The data is accessible at NCBI BioProject: PRJNA566127. These data would be crucial for the identification of genes associated with the compounds exerting pharmaceutical properties and also for molecular marker development.
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OBJECTIVE: The interferon-gamma releasing assay (IGRA) has been widely used to diagnose latent tuberculosis infection (TBI). However, there are limited data on the association between performance in the IGRA and risk of tuberculosis disease (TBD), as well as on the appropriate IGRA threshold for initiating TBI treatment. METHODS: The analysis was performed using the IGRA results in the Korean Military Manpower Administration database (January 2017 to December 2021), and TBD cases reported to the Korean Military Medical Command (January 2017 to June 2023). All Korean candidates for 18-month military service underwent the IGRA in the pre-enlistment examination, and enlistees who tested positive (≥0.35 IU/mL) were advised to receive TBI treatment before enlistment. RESULTS: From 2017 to 2021, 1 647 941 individuals were screened, with 29 574 testing positive for IGRA. Excluding nonenlistees namely individuals with TBD before enlistment, 19 387 individuals were IGRA positive and 1 356 324 IGRA negative. Of the positives, 4351 were excluded due to discontinued or ongoing TBI treatment at or after enlistment. During follow-up of 9219 untreated and 5818 treated positive individuals and 1 356 324 negatives, TBD occurred in 22 of the IGRA-positive individuals (97.5/100 000 person-years [95% CI, 61.1-147.7]), predominantly in the untreated group (18 cases, 130.1/100 000 person-years [95% CI, 77.1-205.7]) compared to the treated group (4 cases, 45.9/100 000 person-years [95% CI 12.5 - 117.4]), whereas 57 cases occurred in the IGRA-negative group (2.8/100 000 person-years [95% CI, 2.2-3.6]). Elevating the cutoff of IGRA from 0.35 IU/mL to 1.33 IU/mL increased positive predictive value (0.2% vs. 0.4%, p 0.03), with insignificant loss of sensitivity (24% vs. 20%, p 0.69) and decreased numbers needing treatment from 790.5 to 415.3. DISCUSSION: Elevated IGRA levels before enlistment are associated with risk of TBD during military service. It is worth considering raising the IGRA threshold for treatment of TBI in cohorts of healthy, young military individuals.
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The incidence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infection is increasing and is associated with vancomycin treatment failures. However, studies investigating the risk factors for treatment failure in hVISA infection are limited. Patients with hVISA bacteremia treated with vancomycin over 7 days between August 2008 and June 2020 were enrolled in this study. Clinical and microbiological characteristics were compared between vancomycin treatment failure and success groups to identify the risk factors for vancomycin treatment failure. Among the 180 patients with hVISA bacteremia, 102 patients treated with vancomycin over 7 days were included. Vancomycin treatment failed in 80 (78%) patients. Patients in the vancomycin treatment failure group were older (P < 0.001) and more frequently had solid cancer (P = 0.04) than those in the vancomycin treatment success group. Solid organ transplantation (SOT) was more frequent (P < 0.001) in the vancomycin treatment success group. The Charlson comorbidity index (P = 0.01) and Acute Physiology and Chronic Health Evaluation II scores (P < 0.001) were higher in the vancomycin treatment failure group. In multivariate analysis, independent risk factors for vancomycin treatment failure were old age and severity of bacteremia. SOT and vancomycin minimal inhibitory concentration (MIC) ≤ 1.0 mg/L using the broth microdilution (BMD) method were associated with successful vancomycin treatment. Old age and infection severity were independent risk factors for vancomycin treatment failure. Vancomycin MIC using the BMD method is an important risk factor for vancomycin treatment failure, and its use should be considered in hVISA bacteremia.IMPORTANCEIn this study, we assessed the clinical and microbiological characteristics of heterogeneous vancomycin-intermediated Staphylococcus aureus (hVISA) bacteremia and identified risk factors for vancomycin treatment failure. We found that advanced age and severity of infection were independent risk factors for vancomycin treatment failure. On the other hand, solid organ transplantation and a low vancomycin minimal inhibitory concentration were associated with successful vancomycin treatment. This study highlights the importance of vancomycin minimal inhibitory concentration in hVISA bacteremia.
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Antibacterianos , Bacteriemia , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas , Staphylococcus aureus , Falha de Tratamento , Vancomicina , Humanos , Vancomicina/uso terapêutico , Vancomicina/efeitos adversos , Masculino , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Feminino , Fatores de Risco , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Pessoa de Meia-Idade , Idoso , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Staphylococcus aureus/efeitos dos fármacos , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Staphylococcus aureus Resistente à Vancomicina/efeitos dos fármacosRESUMO
This study evaluated the determinants of mortality and the T cell immune response in patients with persistent Staphylococcus aureus bacteremia (SAB). This was a prospective cohort study and patients with confirmed SAB were enrolled from 2008 to 2020. We compared clinical, microbiological, and genotypic features between surviving and deceased patients with persistent SAB. The concentrations of cytokines and the proportions of IFN-γ secreting CD4+ T cells were measured serially during the bacteremia period. Of the 1760 patients, 242 had persistent bacteremia (PB), and 49 PB patients died within 30 days. In the multivariate analysis, the APACHE II score and female sex were independently associated with 30 days mortality. The level of IL-10 was significantly increased in the plasma of patients with a high Pitt bacteremia score and those who died within 12 weeks from the index day. The proportion of IFN-γ-secreting CD4+ T cells were the highest just before the positive-to-negative conversion of blood cultures in patients with a low Pitt bacteremia score and those who survived for 12 weeks. The level of IL-10 is correlated with clinical outcomes in PB patients. IFN-γ secreting CD4+ T cells might play a pivotal role in SAB PB.
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Bacteriemia , Linfócitos T CD4-Positivos , Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Masculino , Feminino , Bacteriemia/mortalidade , Bacteriemia/microbiologia , Bacteriemia/imunologia , Linfócitos T CD4-Positivos/imunologia , Infecções Estafilocócicas/mortalidade , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/imunologia , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Estudos Prospectivos , Interferon gama/sangue , Interferon gama/metabolismo , Interleucina-10/sangue , Adulto , Citocinas/sangue , Citocinas/metabolismoRESUMO
INTRODUCTION: Marmosets have been shown to spontaneously develop pathological hallmarks of Alzheimer's disease (AD) during advanced age, including amyloid-beta plaques, positioning them as a model system to overcome the rodent-to-human translational gap for AD. However, Tau expression in the marmoset brain has been understudied. METHODS: To comprehensively investigate Tau isoform expression in marmosets, brain tissue from eight unrelated marmosets across various ages was evaluated and compared to human postmortem AD tissue. Microtubule-associated protein tau ( MAPT ) mRNA expression and splicing were confirmed by RT-PCR. Tau isoforms in the marmoset brain were examined by western blot, mass spectrometry, immunofluorescence, and immunohistochemical staining. Synaptic Tau expression was analyzed from crude synaptosome extractions. RESULTS: 3R and 4R Tau isoforms are expressed in marmoset brains at both transcript and protein levels across ages. Results from western blot analysis were confirmed by mass spectrometry, which revealed that Tau peptides in marmoset corresponded to the 3R and 4R peptides in the human AD brain. 3R Tau was primarily enriched in neonate brains, and 4R enhanced in adult and aged brains. Tau was widely distributed in neurons with localization in the soma and synaptic regions. Phosphorylation residues were observed on Thr-181, Thr-217, and Thr-231, Ser202/Thr205, Ser396/Ser404. Paired helical filament (PHF)-like aggregates were also detected in aged marmosets. DISCUSSION: Our results confirm the expression of both 3R and 4R Tau isoforms and important phosphorylation residues in the marmoset brain. These data emphasize the significance of marmosets with natural expression of AD-related hallmarks as important translational models for the study of AD.