Transmission Hub Research Articles

Sustained Spread of HIV-1 CRF55_01B in Its Place of Initial Origin: Dynamics and Hotspots.

Shenzhen, a city with a substantial mobile population, was identified as the first discovered region of HIV-1 CRF55_01B and epicenter of its severe epidemic. During the implementation of venue-based behavioral interventions and the "treat-all" policy, discerning the spread patterns and transmission hotspots of CRF55_01B is imperative. In this study, 1,450 partial pol sequences, with demographic information, were collected from all newly diagnosed CRF55_01B infections in Shenzhen from 2008 to 2020. Molecular networks were constructed using the maximum likelihood and time-resolve phylogenies. Transmission rates, effective reproduction numbers (Re) of clusters and viral dispersal were evaluated using Bayesian inference. In total, 526 sequences formed 114 clusters, including seven large clusters. The status and size of clusters were strongly correlated with age, ethnicity, occupation and CD4+ T cell counts. The transmission rates of clusters were significantly higher than the national epidemic estimate. Four large clusters had Re exceeding 1 at the end of sampling period. Immigrants from Guangdong and Hunan, along with local residents, were identified as the transmission hubs, with heterosexual men being the main source and MSM being the main destination. The virus exhibited a high movement frequency from individuals aged 30-49 years toward diverse age groups. This study demonstrated the hidden CRF55_01B transmissions continued despite current combined interventions in Shenzhen, and special at-risk individuals susceptible to infection or transmission were identified, potentially serving as targets for more effective prevention and control of the local epidemic, thereby mitigating cross-regional spread nationwide due to population migration.

Carbapenem-resistant Klebsiella pneumoniae capsular types, antibiotic resistance and virulence factors in China: a longitudinal, multi-centre study

Epidemiological knowledge of circulating carbapenem-resistant Klebsiella pneumoniae (CRKP) is needed to develop effective strategies against this public health threat. Here we present a longitudinal analysis of 1,017 CRKP isolates recovered from patients from 40 hospitals across China between 2016 and 2020. Virulence gene and capsule typing revealed expansion of CRKP capsule type KL64 (59.5%) alongside decreases in KL47 prevalence. Hypervirulent CRKP increased in prevalence from 28.2% in 2016 to 45.7% in 2020. Phylogenetic and spatiotemporal analysis revealed Beijing and Shanghai as transmission hubs accounting for differential geographical prevalence of KL47 and KL64 strains across China. Moderate frequency capsule or O-antigen loss was also detected among isolates. Non-capsular CRKP were more susceptible to phagocytosis, attenuated during mouse infections, but showed increased serum resistance and biofilm formation. These findings give insight into CRKP serotype prevalence and dynamics, revealing the importance of monitoring serotype shifts for the future development of immunological strategies against CRKP infections.

Carbapenem-resistant Escherichia coli exhibit diverse spatiotemporal epidemiological characteristics across the globe

Carbapenem-resistant Escherichia coli (CREC) poses a severe global public health risk. This study reveals the worldwide geographic spreading patterns and spatiotemporal distribution characteristics of resistance genes in 7918 CREC isolates belonging to 497 sequence types (ST) and originating from 75 countries. In the last decade, there has been a transition in the prevailing STs from highly virulent ST131 and ST38 to higher antibiotic-resistant ST410 and ST167. The rise of multi-drug resistant strains of CREC carrying plasmids with extended-spectrum beta-lactamase (ESBL) resistance genes could be attributed to three important instances of host-switching events. The spread of CREC was associated with the changing trends in blaNDM-5, blaKPC-2, and blaOXA-48, as well as the plasmids IncFI, IncFII, and IncI. There were intercontinental geographic transfers of major CREC strains. Various crucial transmission hubs and patterns have been identified for ST131 in the United Kingdom, Italy, the United States, and China, ST167 in India, France, Egypt, and the United States, and ST410 in Thailand, Israel, the United Kingdom, France, and the United States. This work is valuable in managing CREC infections and preventing CREC occurrence and transmission inside healthcare settings and among diverse hosts.

To study island China

As greater attention has been paid to island research in China, interactions between Chinese and international island scholars have increased. However, research has tended to take an ‘islands of China’ approach, which perceives China as a continental country surrounded by a large number of islands. The present paper proposes an alternative ‘island China’ perspective, informed by selected Chinese traditions of thinking about islands and the sea, that captures the role islands have played and continue to play in Chinese culture. Drawing upon Fei Xiaotong’s reflexive concept of ‘cultural self-consciousness’, we consider the cultural history of island China, including conceptual tensions between the binaries of continent/island and center/periphery, conceptions of land dwellers and water dwellers, the role of islands as hubs of cultural transmission, and the formation of maritime societies across East and Southeast Asia. We also argue that this cultural history ought to influence island governance in China today.

Identifying critical transmission sectors, paths, and carbon communities for CO2 mitigation in global supply chains

The critical transmission hubs in global supply chain networks have great potential to reduce carbon emissions, yet this has not received much attention from existing studies. This research combines the structural path betweenness, an extended structural path analysis, and a multi-level modularity optimization algorithm to identify key transmission sectors, paths, and carbon communities in a global supply chain network using the environmentally extended multi-regional input-output analysis. The results show that (1) China's metal industry, power industry, and non-metallic industry are the most crucial transmission centers, and some sectors, such as the paper industry and textile industry in China, are also key transmission hubs, yet they are ignored by traditional accounting methods. From a national viewpoint, China is the most key transmission hub, and its high betweenness is mainly caused by domestic demand. Meanwhile, the CO2 emissions transferred by China to satisfy foreign demand are mainly related to the US, ROW (especially the Asia-Pacific region), and Japan. (2) The transmitted carbon emission is mainly concentrated in the first four production layers, accounting for 69.46 % of the total. (3) The global carbon emission network can be divided into 20 carbon communities. And the largest communities are mainly led by mainland China. Most of the communities contain various national sectors, which offer evidence for international cooperation strategies. The results offer policymakers a new perspective on mitigating environmental stress.

A High-Flexibility CAN-TSN Gateway With a Low-Congestion TSN-to-CAN Scheduler

The network architecture with controller area network (CAN) as the domain bus in most domains and timesensitive networking (TSN) as the backbone network is called the CAN-TSN interconnection network architecture, which has been or will be employed in industrial embedded networks (e.g., automobiles, spacecraft, and factory automation). In this architecture, the CAN-TSN gateway acts as a transmission hub handling a large number of communications between the CAN domains and TSN. However, most commercial CAN-TSN gateways are highly integrated with low flexibility, such that they are hard to accommodate different time planning mechanisms from TSN. In addition, these CAN-TSN gateways suffer from high congestion when TSN frames are sent from the TSN side to a CAN domain (i.e., TSN-to-CAN transmission) because of at least 100 times in the transmission rate between CAN and TSN. In this study, we propose a high-flexibility CAN-TSN gateway, where the CAN side can be easily adapted to different bus protocols, and the TSN side can be easily adapted to different configurations. In the gateway, we develop a low-congestion TSN-to-CAN scheduler, which executes a maximum awaiting time (MAT)-based scheduling strategy to alleviate the congestion. Experiments on the prototype platform show the advantages of the proposed CAN-TSN gateway and the developed MAT-based scheduling strategy.

Dispersal history and bidirectional human-fish host switching of invasive, hypervirulent Streptococcus agalactiae sequence type 283.

Human group B Streptococcus (GBS) infections attributable to an invasive, hypervirulent sequence type (ST) 283 have been associated with freshwater fish consumption in Asia. The origin, geographic dispersion pathways and host transitions of GBS ST283 remain unresolved. We gather 328 ST283 isolate whole-genome sequences collected from humans and fish between 1998 and 2021, representing eleven countries across four continents. We apply Bayesian phylogeographic analyses to reconstruct the dispersal history of ST283 and combine ST283 phylogenies with genetic markers and host association to investigate host switching and the gain and loss of antimicrobial resistance and virulence factor genes. Initial dispersal within Asia followed ST283 emergence in the early 1980s, with Singapore, Thailand and Hong Kong observed as early transmission hubs. Subsequent intercontinental dispersal originating from Vietnam began in the decade commencing 2001, demonstrating ST283 holds potential to expand geographically. Furthermore, we observe bidirectional host switching, with the detection of more frequent human-to-fish than fish-to-human transitions, suggesting that sound wastewater management, hygiene and sanitation may help to interrupt chains of transmission between hosts. We also show that antimicrobial resistance and virulence factor genes were lost more frequently than gained across the evolutionary history of ST283. Our findings highlight the need for enhanced surveillance, clinical awareness, and targeted risk mitigation to limit transmission and reduce the impact of an emerging pathogen associated with a high-growth aquaculture industry.

Isolation, identification, and pathogenicity of porcine epidemic diarrhea virus.

Porcine epidemic diarrhea (PED) is an enterophilic infectious disease caused by the porcine epidemic diarrhea virus (PEDV), which can lead to dehydration-like diarrhea in piglets with a mortality rate of up to 100%, causing huge economic losses to the global pig industry. In this study, we isolated two PEDV strains, FS202201 and JY202201, from diarrheal samples collected from two new PED outbreak farms in 2022. We performed phylogenetic analysis of the S gene and whole gene sequence. The effects of the different mutations on viral pathogenicity were investigated using piglet challenge experiments. The results showed that both strains belong to the G2c subtype, a widely prevalent virulent strain. Compared with FS202201, JY202201 harbored substitution and deletion mutations in nsp1. Both FS202201 and JY202201 infected piglets showed severe diarrhea and significant intestinal tissue lesions at an infection dose of 104 TCID50/mL, with a mortality rate of 50%; however, JY202201 required an additional day to reach mortality stabilization. An infection dose of 103 TCID50/mL reduced diarrhea and intestinal tissue lesions in piglets, with mortality rates of the two strains at 16.7% and 0%, respectively. In addition, PEDV was detected in the heart, liver, spleen, lungs, kidneys, mesenteric lymph nodes, stomach, large intestine, duodenum, jejunum, and ileum, with the highest levels in the intestinal tissues. In conclusion, this study enriches the epidemiology of PEDV and provides a theoretical basis for the study of its pathogenic mechanism and prevention through virus isolation, identification, and pathogenicity research on newly identified PED in the main transmission hub area of PEDV in China (Guangdong).

Conservation measures or hotspots of disease transmission? Agri-environment schemes can reduce disease prevalence in pollinator communities.

Insects are under pressure from agricultural intensification. To protect pollinators, conservation measures such as the EU agri-environment schemes (AES) promote planting wildflowers along fields. However, this can potentially alter disease ecology by serving as transmission hubs or by diluting infections. We tested this by measuring plant-pollinator interactions and virus infections (DWV-A, DWV-B and ABPV) across pollinator communities in agricultural landscapes over a year. AES had a direct effect on DWV-B, reducing prevalence and load in honeybees, with a tentative general dilution effect on load in early summer. DWV-A prevalence was reduced both under AES and with increasing niche overlap between competent hosts, likely via a dilution effect. By contrast, AES had no impact on ABPV, its prevalence driven by the proportion of bumblebees in the community. Epidemiological differences were also reflected in the virus phylogenies, with DWV-B showing recent rapid expansion, while DWV-A and ABPV showed slower growth rates and geographical population structure. Phylogenies indicate that all three viruses freely circulate across their host populations. Our study illustrates how complex interactions between environmental, ecological and evolutionary factors may influence wildlife disease dynamics. Supporting pollinator nutrition can mitigate the transmission of important bee diseases, providing an unexpected boost to pollinator conservation. This article is part of the theme issue 'Infectious disease ecology and evolution in a changing world'.

Infectious disease ecology and evolution in a changing world.

Infectious disease ecology and evolution in a changing world.

Remote Patient Monitoring for Hypertension: Feasibility and Outcomes of a Clinic-Based Pilot in a Minority Population.

In the US 48% of adults have hypertension, with direct costs in excess of $130 billion per year. Remote patient monitoring (RPM) has been discussed as a useful tool in the treatment of hypertension, but few studies evaluate its cost effectiveness or efficacy in minority, lower socio-economic (SES) populations. Our study aims to evaluate the clinical and financial outcomes of RPM in hypertension management in a primarily minority, low-SES population. In this prospective cohort pilot study, patients with uncontrolled primary hypertension (defined via Joint National Committee 8 guidelines) were randomly selected from a single academically affiliated primary care clinic. Patients were enrolled on a rolling basis for 90 days. Patients were given blood pressure cuffs and transmission hubs and asked to transmit daily blood pressure readings. Patients were called weekly by research assistants and concerns were escalated to the primary care physician. The control group was the remaining 299 uncontrolled hypertensive patients from the same clinic population analyzed via retrospective chart records at the conclusion of the interventional study period. The primary outcome was blood pressure control. Secondary outcomes were relative improvement in systolic pressure and direct costs. A total of 13 patients were enrolled into the RPM intervention; these patients were 54% female, 100% African American, and 77% Medicaid. When assessed via intention-to-treat analysis, patients in the intervention group had non-inferior blood pressure control at 90 days (46% experimental vs 31% control, P = .33) and average change in systolic blood pressure at 90 days (13.5 vs 3.7 mmHg, P = .174) while experiencing a significant reduction in office-based visits at 90 days (1.5 vs 5.9, P < .001) as compared to control. Results on per-protocol analysis also showed non-inferior BP control (63% vs 31%, P = .135). Financially, the program generated margins of $29 per patient at 90 days. Patients in our minority- and Medicaid-predominant cohort achieved noninferior blood pressure control as compared to retrospective control at 90 days and a significant reduction in all-cause clinic visits at 90 days. The program generated little revenue per patient, with main barriers to implementation including patient compliance and payor denial.

The Role of Location in the Spread of SARS-CoV-2: Examination of Cases and Exposed Contacts in South Texas, Using Social Network Analysis.

This study sought to better understand the types of locations that serve as hubs for the transmission of COVID-19. Contact tracers interviewed individuals who tested positive for SARS-CoV-2 between November 2020 and March 2021, as well as the people with whom those individuals had contact. We conducted a 2-mode social network analysis of people by the types of places they visited, focusing on the forms of centrality exhibited by place types. The most exposed locations were grocery stores, commercial stores, restaurants, commercial services, and schools. These types of locations also have the highest "betweenness," meaning that they tend to serve as hubs between other kinds of locations since people would usually visit more than 1 location in a day or when infected. The highest pairs of locations were grocery store/retail store, restaurant/retail store, and restaurant/grocery store. Schools are not at the top but are 3 times in the top 7 pairs of locations and connected to the 3 types of locations in those top pairs. As the pandemic progressed, location hotspots shifted between businesses, schools, and homes. In this social network analysis, certain types of locations appeared to be potential hubs of transmission.

MCTSR: A super‐resolution method for defects in gas‐insulated switchgear X‐ray images based on multi‐scale contextual transformers

AbstractAs the core equipment of transmission and distribution hubs, the operational status of gas‐insulated switchgear (GIS) is closely linked to the safety of the power system. Recently, X‐ray digital imaging technology has been extensively used in GIS equipment fault detection. However, the X‐ray image of GIS is blurred, which is not conducive to the detection of tiny defects. Thus, a super‐resolution method for GIS X‐ray images based on multi‐scale context transformers is proposed in this study, namely MCTSR. Firstly, a second‐order image degradation model is introduced to generate GIS X‐ray low‐resolution images that more closely resemble the real world. Secondly, a contextual transformer gate module is constructed to improve attention to tiny defects in GIS X‐ray images. Thirdly, a U‐Net discriminator network based on multi‐scale contextual transformers is intended to enrich the information of the generated images. Finally, the proposed discriminator is combined with the existing generator to compose a super‐resolution method applicable to GIS X‐ray images. The experimental results demonstrate that the method outperforms other methods in peak signal‐to‐noise ratio and structural similarity on the constructed GIS X‐ray image dataset. In addition, the output image of the proposed method facilitates the subsequent defect detection.

Evidence for flock transmission of individual subtypes and strains of avian influenza viruses: A monitoring study of wild birds in Kazakhstan

An active surveillance study of avian influenza viruses (AIVs) in wild birds was carried out in Kazakhstan in 2018–2019. In total, 866 samples were collected from wild birds and analyzed for influenza viruses using molecular and virological tests. Genome segments of Asian, European, and Australian lineages were detected in 25 (4.6%) out of 541 waterfowl samples positive for subtype H3N8, and in two (0.6%) out of 325 H3N8 positive samples from terrestrial birds. No highly pathogenic avian influenza virus (AIV) was detected.The results indicated transmission of closely related strains or identical subtypes of AIVs by a flock-unit of migratory birds or annual cyclical pattern of subtype dominance. The simultaneous circulation of genome segments of the Asian, European and Australian genetic lineages of H3N8 AIVs in wild birds in Kazakhstan indicated the important role of Central Asia as a transmission hub of AI viruses linking the East Asian migratory flyways with European flyways and vice versa.

Comparative Dynamics of Delta and Omicron SARS-CoV-2 Variants across and between California and Mexico.

Evolutionary analysis using viral sequence data can elucidate the epidemiology of transmission. Using publicly available SARS-CoV-2 sequence and epidemiological data, we developed discrete phylogeographic models to interrogate the emergence and dispersal of the Delta and Omicron variants in 2021 between and across California and Mexico. External introductions of Delta and Omicron in the region peaked in early July (2021-07-10 [95% CI: 2021-04-20, 2021-11-01]) and mid-December (2021-12-15 [95% CI: 2021-11-14, 2022-01-09]), respectively, 3 months and 2 weeks after first detection. These repeated introductions coincided with domestic migration events with no evidence of a unique transmission hub. The spread of Omicron was most consistent with gravity centric patterns within Mexico. While cross-border events accounted for only 5.1% [95% CI: 4.3–6] of all Delta migration events, they accounted for 20.6% [95% CI: 12.4–29] of Omicron movements, paralleling the increase in international travel observed in late 2021. Our investigations of the Delta and Omicron epidemics in the California/Mexico region illustrate the complex interplay and the multiplicity of viral and structural factors that need to be considered to limit viral spread, even as vaccination is reducing disease burden. Understanding viral transmission patterns may help intra-governmental responses to viral epidemics.

Characterizing genetic transmission networks among newly diagnosed HIV-1 infected individuals in eastern China: 2012-2016.

We aimed to elucidate the characteristics of HIV molecular epidemiology and identify transmission hubs in eastern China using genetic transmission network and lineage analyses. HIV-TRACE was used to infer putative relationships. Across the range of epidemiologically-plausible genetic distance (GD) thresholds (0.1–2.0%), a sensitivity analysis was performed to determine the optimal threshold, generating the maximum number of transmission clusters and providing reliable resolution without merging different small clusters into a single large cluster. Characteristics of genetically linked individuals were analyzed using logistic regression. Assortativity (shared characteristics) analysis was performed to infer shared attributes between putative partners. 1,993 persons living with HIV-1 were enrolled. The determined GD thresholds within subtypes CRF07_BC, CRF01_AE, and B were 0.5%, 1.2%, and 1.7%, respectively, and 826 of 1,993 (41.4%) sequences were linked with at least one other sequence, forming 188 transmission clusters of 2–80 sequences. Clustering rates for the main subtypes CRF01_AE, CRF07_BC, and B were 50.9% (523/1027), 34.2% (256/749), and 32.1% (25/78), respectively. Median cluster sizes of these subtypes were 2 (2–52, n = 523), 2 (2–80, n = 256), and 3 (2–6, n = 25), respectively. Subtypes in individuals diagnosed and residing in Hangzhou city (OR = 1.423, 95% CI: 1.168–1.734) and men who have sex with men (MSM) were more likely to cluster. Assortativity analysis revealed individuals were more likely to be genetically linked to individuals from the same age group (AIage = 0.090, P<0.001) and the same area of residency in Zhejiang (AIcity = 0.078, P<0.001). Additionally, students living with HIV were more likely to be linked with students than show a random distribution (AI student = 0.740, P<0.01). These results highlight the importance of Hangzhou City in the regional epidemic and show that MSM comprise the population rapidly transmitting HIV in Zhejiang Province. We also provide a molecular epidemiology framework for improving our understanding of HIV transmission dynamics in eastern China.

Flower sharing and pollinator health: a behavioural perspective.

Disease is an integral part of any organisms' life, and bees have evolved immune responses and a suite of hygienic behaviours to keep them at bay in the nest. It is now evident that flowers are another transmission hub for pathogens and parasites, raising questions about adaptations that help pollinating insects stay healthy while visiting hundreds of plants over their lifetime. Drawing on recent advances in our understanding of how bees of varying size, dietary specialization and sociality differ in their foraging ranges, navigational strategies and floral resource preferences, we explore the behavioural mechanisms and strategies that may enable foraging bees to reduce disease exposure and transmission risks at flowers by partitioning overlapping resources in space and in time. By taking a novel behavioural perspective, we highlight the missing links between disease biology and the ecology of plant-pollinator relationships, critical for improving the understanding of disease transmission risks and the better design and management of habitat for pollinator conservation. This article is part of the theme issue 'Natural processes influencing pollinator health: from chemistry to landscapes'.

Phylodynamic Dispersal of SARS-CoV-2 Lineages Circulating across Polish-German Border Provinces.

Introduction: The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has evolved into a worldwide outbreak, with significant molecular evolution over time. Large-scale phylodynamic studies allow to map the virus spread and inform preventive strategies. Aim: This study investigates the extent of binational dispersal and dynamics of SARS-CoV-2 lineages between seven border provinces of the adjacent countries of Poland and Germany to reconstruct SARS-CoV-2 transmission networks. Methods: Following three pandemic waves from March 2020 to the end of May 2021, we analysed a dataset of 19,994 sequences divided into B.1.1.7|Alpha and non-Alpha lineage groups. We performed phylogeographic analyses using the discrete diffusion models to identify the pathways of virus spread. Results: Based on population dynamics inferences, in total, 673 lineage introductions (95% HPD interval 641–712) for non-Alpha and 618 (95% HPD interval 599–639) for B.1.1.7|Alpha were identified in the area. For non-Alpha lineages, 5.05% binational, 86.63% exclusively German, and 8.32% Polish clusters were found, with a higher frequency of international clustering observed for B.1.1.7|Alpha (13.11% for binational, 68.44% German and 18.45% Polish, p < 0.001). We identified key transmission hubs for the analysed lineages, namely Saxony, West Pomerania and Lower Silesia. Conclusions: Clustering patterns between Poland and Germany reflect the viral variant transmission dynamics at the international level in the borderline area. Tracing the spread of the virus between two adjacent large European countries may provide a basis for future intervention policies in cross-border cooperation efforts against the spread of the pandemics.

Research Progress on the Relationship between Peripheral Somatosensory Neurons and Autism Spectrum Disorder

The incidence of autism spectrum disorder (ASD) is increasing year by year worldwide and has become a global public health problem. Many studies showed that there was a close relationship between peripheral somatosensory neuron dysfunction and the pathogenesis of ASD. This article summarizes the research from domestic and foreign of the relationship between peripheral somatosensory neurons and autism spectrum disorder at home and abroad, mainly from the relationship between somatosensory neuron function and human growth and development, somatosensory disorders, the main influencing factors, and the shortcomings and prospects of research. Peripheral somatosensory neurons are the primary processing centers in somatosensory neural pathways and important information transmission hubs, which are essential for the formation of somatosensory perception; their information transmission with the brain has an important impact on brain development, the development of various complex behaviors and emotions. The influencing factors include genetic and environmental factors, of which genetic factors include γ-aminobutyric acid type A receptor subunit β3 gene mutation, methylated CpG binding protein 2 gene loss or mutation, SHANK3 gene mutation, Fmr1 gene deletion, Cntnap2 gene deletion; environmental factors such as infection, drugs, stress, and obesity. Peripheral somatosensory neurons are important dysfunction sites in the sensory disorder phenotype. Targeting peripheral somatosensory neurons may provide new strategies for somatosensory abnormalities and ASD treatment. However, due to the diversity of clinical manifestations of ASD, differences in different pathogenic genes and pathogenesis, and the high diversity of sensory interneurons in the spinal dorsal horn, the next step still needs to be in-depth study on the application of peripheral somatosensory neurons in ASD, and further clarify its internal mechanism.

Amyloid‐β and tau pathologies relate to distinctive brain dysconnectomics in autosomal‐dominant Alzheimer’s disease

AbstractBackgroundAlzheimer’s disease (AD)‐related pathology (i.e., amyloid‐β and neurofibrillary tangles) disrupts functional networks that support higher‐order cognitive functions. Yet, it is not well known how the brain’s functional architecture is differentially associated with in vivo pathology in preclinical AD, which is critical for predicting disease risk and progression. We intersected functional connectivity and PET images to examine how in vivo amyloid‐β and tau pathologies are associated with weighted‐degree centrality patterns, known to be important for understanding network organization and information transmission hubs, in cognitively‐unimpaired individuals with autosomal‐dominant AD due to the Presenilin‐1 (PSEN‐1) E280A mutation.Method21 cognitively‐unimpaired PSEN1 E280A carriers and 31 non‐carriers underwent resting‐state fMRI, 11C Pittsburgh compound B‐PET and 18F Flortaucipir‐PET. We used graph‐based network analyses to examine weighted‐degree centrality, the sum of weights from edges connecting to a node. A general linear model was used to compare connectivity maps between groups, and partial correlations were used to examine the relationship between individual‐subject maps with whole‐brain amyloid‐β and tau PET. A significance threshold of p&lt;0.05 was used. Analyses were covaried for age and corrected for multiple comparisons.ResultCompared to non‐carriers, mutation carriers exhibited reduced weighted‐degree in the medial occipitoparietal and posterior cingulate cortices. Greater amyloid‐β was associated with reduced weighted‐degree in the lateral temporal lobe and fusiform gyrus, and greater weighted‐degree in the lateral and medial prefrontal cortices. In turn, greater tau burden was associated with greater weighted‐degree in the lateral and medial temporal regions, anterior and posterior cingulate cortices, lateral parietal cortex and precuneus, and decreased weighted‐degree in dorsomedial prefrontal cortex.ConclusionOur findings show that cognitively‐unimpaired individuals who are genetically‐determined to develop AD dementia in their forties have abnormal patterns of functional connectivity that resemble spatial patterns of amyloid‐β and tau propagation. Regions that had weaker connections with nearby and distant regions showed greater amyloid‐β burden, while regions that were highly functionally connected exhibited greater tau burden, which has been suggested to increase the probability of tau seeding and propagation. These findings contribute to our understanding of how functional connectivity patterns can help predict risk and monitor AD progression from preclinical to clinical stages.