Featured
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| Open AccessMaternal carriage of Prevotella during pregnancy associates with protection against food allergy in the offspring
Incidence of food allergy in westernized populations is associated with low abundance of Prevotella. Here, the authors analyse the microbiome of a mother-infant prebirth cohort and find that maternal carriage, but not infant carriage, of P. copri during pregnancy predicts the absence of food allergy in the offspring.
- Peter J. Vuillermin
- , Martin O’Hely
- & Esther Bandala Sanchez
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Article
| Open AccessStronger policy required to substantially reduce deaths from PM2.5 pollution in China
Chinese government has implemented the air pollution control measure-the Air Pollution Prevention and Control Action Plan in 2013, whose effects have not been fully studied. Here the authors show that from 2013 to 2017, the plan has achieved substantial public health benefits.
- Huanbi Yue
- , Chunyang He
- & Brett A. Bryan
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Article
| Open AccessGlobal consumption and international trade in deforestation-associated commodities could influence malaria risk
Because many primary commodities cause deforestation and deforestation can increase malaria transmission, international trade can thus indirectly influence malaria risk. Here the authors use trade databases for commodites associated with deforestation to demonstrate that consumption of such commodities in developed nations could increase malaria risk in developing nations.
- Leonardo Suveges Moreira Chaves
- , Jacob Fry
- & Manfred Lenzen
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Article
| Open AccessAnalysis of DNA methylation associates the cystine–glutamate antiporter SLC7A11 with risk of Parkinson’s disease
Parkinson’s disease (PD) is a common neurodegenerative disorder with a complex etiology involving genetics and the environment. Here, Vallerga et al. identify two CpG probes associated with PD in a blood cell type-corrected epigenome-wide meta-analysis, implicating the SLC7A11 gene as a plausible biological target.
- Costanza L. Vallerga
- , Futao Zhang
- & Jacob Gratten
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Article
| Open AccessThe role of sex work laws and stigmas in increasing HIV risks among sex workers
HIV incidence among sex workers remains high in many settings. Here, the authors utilize individual-level data across ten countries in sub-Saharan Africa and suggest that increasingly punitive and non-protective laws are associated with HIV, and that stigmas and sex work laws may operate jointly in increasing HIV risk.
- Carrie E. Lyons
- , Sheree R. Schwartz
- & Stefan Baral
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Article
| Open AccessMaternal paraben exposure triggers childhood overweight development
Parabens are preservatives widely used in consumer products including cosmetics and food. Here the authors demonstrate that maternal paraben exposure may contribute to childhood overweight development by an altered neuronal appetite regulation.
- Beate Leppert
- , Sandra Strunz
- & Tobias Polte
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Article
| Open AccessGenomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke
Stroke risk is influenced by genetic and lifestyle factors and previously a genomic risk score (GRS) for stroke was proposed, albeit with limited predictive power. Here, Abraham et al. develop a metaGRS that is composed of several stroke-related GRSs and demonstrate improved predictive power compared with individual GRS or classic risk factors.
- Gad Abraham
- , Rainer Malik
- & Martin Dichgans
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Article
| Open AccessHigh-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program
Prostate cancer progression may be enhanced by a high-fat diet. Here the authors show that a diet high in saturated fats enhance the MYC-driven transcriptional program, a feature that independently predicts prostate cancer progression and death.
- David P. Labbé
- , Giorgia Zadra
- & Myles Brown
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Article
| Open AccessAgricultural land-uses consistently exacerbate infectious disease risks in Southeast Asia
Here, Shah et al. perform a meta-analysis and show that people who live or work in agricultural land in Southeast Asia are on average 1.7 times more likely to be infected with a pathogen than controls, suggesting that agricultural land-use increases infectious disease risk.
- Hiral A. Shah
- , Paul Huxley
- & Kris A. Murray
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Article
| Open AccessBridging of Neisseria gonorrhoeae lineages across sexual networks in the HIV pre-exposure prophylaxis era
Here, Williamson et al. combine epidemiological and genomic analysis of 2,186 Neisseria gonorrhoeae isolates from Australia and show that men who have sex with men and women are a possible ‘bridging’ population between men who have sex with men and heterosexuals.
- Deborah A. Williamson
- , Eric P. F. Chow
- & Benjamin P. Howden
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Article
| Open AccessAir pollution exposure associates with increased risk of neonatal jaundice
Air pollution has become a major health risk in China. Here Zhang et al. report that maternal and neonatal exposure to particulate matter increases the risk of neonatal jaundice based on the study of 25,782 newborns born in China between 2014 and 2017.
- Liqiang Zhang
- , Weiwei Liu
- & Yanhong Wang
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Article
| Open AccessA meta-analysis of genome-wide association studies identifies multiple longevity genes
Genome-wide association studies have only revealed a handful of genetic loci for longevity. Here, in a case–control design based on phenotype definitions of individuals surviving at or beyond the age corresponding to the 90th and 99th survival percentile, the authors report two additional loci located in the APOE locus and near GPR78.
- Joris Deelen
- , Daniel S. Evans
- & Joanne M. Murabito
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Article
| Open AccessGWAS for urinary sodium and potassium excretion highlights pathways shared with cardiovascular traits
Levels of sodium and potassium in urine are associated with cardiovascular traits. Here, Pazoki et al. perform genome-wide association studies for urinary sodium and potassium secretion and identify 50 and 13 novel loci, respectively, some of which show a potential causal relationship with blood pressure based on MR analysis.
- Raha Pazoki
- , Evangelos Evangelou
- & Abbas Dehghan
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Article
| Open AccessGenetic risk for autoimmunity is associated with distinct changes in the human gut microbiome
HLA alleles and microbiome alterations have been separately associated with human autoimmunity. Here the authors identify differences in stool microbiome between healthy carriers of HLA alleles conferring low- and high-risk for type 1 diabetes, suggesting that HLA shaping of microbiome may contribute to HLA impact on autoimmunity risks.
- Jordan T. Russell
- , Luiz F. W. Roesch
- & Johnny Ludvigsson
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Article
| Open AccessTens of thousands additional deaths annually in cities of China between 1.5 °C and 2.0 °C warming
Heatwaves are expected to increase under climate change, and so are the associated deaths. Here the authors determine the regional high temperature thresholds for 27 metropolises in China and analyze the changes to heat-related mortality, showing that the additional global-warming temperature increase of 0.5°C, from 1.5°C to 2.0°C, will lead to tens of thousands of additional deaths, annually.
- Yanjun Wang
- , Anqian Wang
- & Thomas Fischer
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Article
| Open AccessAnalysis of polygenic risk score usage and performance in diverse human populations
Predominant participation of European-ancestry individuals in genetic studies has hindered the better understanding of genetic risk in non-European ancestry individuals. Here, Duncan et al. quantify polygenic risk score use and performance in worldwide populations.
- L. Duncan
- , H. Shen
- & B. Domingue
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Article
| Open AccessMendelian randomization analysis using mixture models for robust and efficient estimation of causal effects
Mendelian randomization (MR) is a powerful and widely used method for causal inference leveraging genetic information. Here, the authors develop MRMix, an MR method using mixture models for more robust and efficient estimation of causal effects.
- Guanghao Qi
- & Nilanjan Chatterjee
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Article
| Open AccessCervicovaginal microbiota and local immune response modulate the risk of spontaneous preterm delivery
Here, Elovitz et al. investigate associations between cervicovaginal microbiota (CVM) and spontaneous preterm birth (sPTB) in a large cohort of African American and non-African American women, and find that CVM and local immune response early in pregnancy are associated with sPTB in an ethnicity-dependent manner.
- Michal A. Elovitz
- , Pawel Gajer
- & Jacques Ravel
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Article
| Open AccessEffects of infection history on dengue virus infection and pathogenicity
Lack of knowledge of individual infection history hinders understanding of immunological interactions among DENV serotypes. Here, the authors introduce a framework to infer the relationship between unobserved infection history and subsequent infection and disease risk, and find complex dependencies.
- Tim K. Tsang
- , Samson L. Ghebremariam
- & Yang Yang
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Review Article
| Open AccessAdvancing environmental exposure assessment science to benefit society
How can scientists and policymakers work together to reduce the health impacts of air pollution? In this review paper, the authors discuss the interplay between advances in environmental exposure assessment and policy advances to tackle pollution in a focused way.
- Andrew Caplin
- , Masoud Ghandehari
- & George Thurston
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Article
| Open AccessGenome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates
Sleep is essential for homeostasis and insufficient or excessive sleep are associated with adverse outcomes. Here, the authors perform GWAS for self-reported habitual sleep duration in adults, supported by accelerometer-derived measures, and identify genetic correlation with psychiatric and metabolic traits
- Hassan S. Dashti
- , Samuel E. Jones
- & Richa Saxena
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Article
| Open AccessMulti-cohort study identifies social determinants of systemic inflammation over the life course
Here, the authors explore the relationship between socioeconomic position (SEP) across the life course and inflammation in a multi-cohort study and show that educational attainment is most strongly related to inflammation, suggesting that socioeconomic disadvantage in young adulthood is independently associated with later life inflammation.
- Eloïse Berger
- , Raphaële Castagné
- & Michelle Kelly-Irving
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Article
| Open AccessLongevity defined as top 10% survivors and beyond is transmitted as a quantitative genetic trait
While human lifespan is only moderately heritable, “getting old” runs in families. Here, van den Berg et al. study mortality data from three-generation cohorts to define a threshold for longevity and find that individuals have an increasing survival advantage with each additional relative in the top 10% survivors of their birth cohort.
- Niels van den Berg
- , Mar Rodríguez-Girondo
- & P. Eline Slagboom
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Article
| Open AccessGenome-wide meta-analysis implicates mediators of hair follicle development and morphogenesis in risk for severe acne
Acne vulgaris is a chronic inflammation of the skin, the genetic basis of which is incompletely understood. Here, Petridis et al. perform GWAS and meta-analysis for acne in 26,722 individuals and identify 12 novel risk loci that implicate structure and maintenance of the skin in severe acne risk.
- Christos Petridis
- , Alexander A. Navarini
- & Michael A. Simpson
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Article
| Open AccessPaternal grandfather’s access to food predicts all-cause and cancer mortality in grandsons
Nutritional experience can have phenotypic consequences in subsequent generations, as is evident from studies in animals and plants. Here, Vågerö et al. find in a large three-generation cohort that access to food in the paternal grandfather associates with all-cause and cancer mortality in male grandchildren.
- Denny Vågerö
- , Pia R. Pinger
- & Gerard J. van den Berg
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Article
| Open AccessAir quality co-benefits for human health and agriculture counterbalance costs to meet Paris Agreement pledges
Local air quality co-benefits can provide convincing support for climate action. Here the authors revisited air quality co-benefits of climate action in the context of NDCs and found that 71–99 thousand premature deaths can be avoided each year by 2030, offsetting the climate mitigation costs on a global level.
- Toon Vandyck
- , Kimon Keramidas
- & Bert Saveyn
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Article
| Open AccessThe gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD
Infants born to obese mothers have altered microbiome and increased risk of obesity and NAFLD. Here the authors establish causality by showing that maternal obesity-shaped infant gut microbiome induces macrophage dysfunction, inflammation, and diet-induced metabolic disease in germ-free mice.
- Taylor K. Soderborg
- , Sarah E. Clark
- & Jacob E. Friedman
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Article
| Open AccessLarge-scale whole-exome sequencing association studies identify rare functional variants influencing serum urate levels
Elevated serum urate levels are a risk factor for gout. Here, Tin et al. perform whole-exome sequencing in 19,517 individuals and detect low-frequency genetic variants in urate transporter genes, SLC22A12 and SLC2A9, associated with serum urate levels and confirm their damaging nature in vitro and in silico.
- Adrienne Tin
- , Yong Li
- & Anna Köttgen
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Article
| Open AccessGWAS for Interleukin-1β levels in gingival crevicular fluid identifies IL37 variants in periodontal inflammation
IL-1β in gingival crevicular fluid (GCF) is a marker of inflammation in periodontal disease. Here, Offenbacher et al. identify genetic variants in the IL37 locus associated with GCF-IL-1β and show that the IL-1β-increasing allele at rs3811046 leads to an enhanced inflammatory response in vitro and in vivo.
- Steven Offenbacher
- , Yizu Jiao
- & Kari E. North
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Article
| Open AccessA study paradigm integrating prospective epidemiologic cohorts and electronic health records to identify disease biomarkers
Biomarker identification requires prohibitively large cohorts with gene expression and phenotype data. The approach introduced here learns polygenic predictors of expression from genetic and expression data, used to infer biomarker levels in patients with genetic and disease information.
- Jonathan D. Mosley
- , QiPing Feng
- & Dan M. Roden
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Article
| Open AccessUnperturbed expression bias of imprinted genes in schizophrenia
This study analyzes allelic expression bias in post-mortem brains of healthy individuals and those diagnosed with schizophrenia or bipolar disorder. The study shows that the number of imprinted genes is consistent with low estimates, and that allelic bias is independent of psychiatric disease status.
- Attila Gulyás-Kovács
- , Ifat Keydar
- & Andrew Chess
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Article
| Open AccessElucidating the genetic basis of social interaction and isolation
Little is known about the genetic determinants of social isolation and loneliness despite their well-established importance for health. Here, using multi-trait GWAS, Day et al. identify 15 genomic loci for loneliness and further show a bidirectional causal relationship between BMI and loneliness by MR.
- Felix R. Day
- , Ken K. Ong
- & John R. B. Perry
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Article
| Open AccessA multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci
Primary open-angle glaucoma (POAG) leads to progressive vision loss. Here, Choquet et al. perform genome-wide association analysis for POAG in a multi-ethnic cohort, identify a total of nine novel genetic loci and show relevant function of FMNL2 and LMX1B using cell line and mouse experiments.
- Hélène Choquet
- , Seyyedhassan Paylakhi
- & Eric Jorgenson
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Article
| Open AccessThe multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression
ELL2 was recently discovered as a susceptibility gene for multiple myeloma (MM). Here, they show that the MM risk allele lowers ELL2 expression in plasma cells, that it also upregulates gene sets related to ribosome biogenesis, and that one of the linked variants reduces binding of MAFF/G/K family transcription factors.
- Mina Ali
- , Ram Ajore
- & Björn Nilsson
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Article
| Open AccessGWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21
Childhood acute lymphoblastic leukemia is common in Latino Americans. Here, the authors conduct a genome-wide association study in a Californian cohort containing children of Latino heritage, and identify loci on 17q12 and 8q24 which may affect hematopoietic and growth-regulation pathways.
- Joseph L. Wiemels
- , Kyle M. Walsh
- & Xiaomei Ma
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Article
| Open AccessGenome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
Vitamin D deficiency is associated with multiple human pathologic conditions. In a genome-wide association study of 79,366 individuals, Jiang et al. replicate four and identify two new genetic loci for serum levels of 25-hydroxyvitamin D and find evidence for a shared genetic basis with autoimmune diseases.
- Xia Jiang
- , Paul F. O’Reilly
- & Douglas P. Kiel
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Article
| Open AccessCausal associations between risk factors and common diseases inferred from GWAS summary data
Genetic methods are useful to test whether risk factors are causal for or consequence of disease. Here, Zhu et al. develop a generalized summary-based Mendelian Randomization (GSMR) method which uses summary-level data from GWAS to test for causal associations of health risk factors with common diseases.
- Zhihong Zhu
- , Zhili Zheng
- & Jian Yang
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Article
| Open AccessA large multi-ethnic genome-wide association study identifies novel genetic loci for intraocular pressure
Intraocular pressure (IOP) is a major risk factor for glaucoma. Here, Choquet and co-authors perform a multi-ethnic genome-wide association study of repeat IOP measurements in 69,756 individuals and identify 40 novel loci, 36 of which show directionally consistent effects in glaucoma.
- Hélène Choquet
- , Khanh K. Thai
- & Eric Jorgenson
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Article
| Open AccessCentral insulin modulates food valuation via mesolimbic pathways
The influence of insulin on food preference and the corresponding underlying neural circuits are unknown in humans. Here, the authors show that increasing insulin changes food preference by modulating mesolimbic neural circuits, and that this pattern is changed in insulin-resistant individuals.
- Lena J. Tiedemann
- , Sebastian M. Schmid
- & Stefanie Brassen
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Article
| Open AccessGenetic loci associated with heart rate variability and their effects on cardiac disease risk
Heart rate variability (HRV) describes the individual variation in cardiac cycle duration and is a measure of vagal control of heart rate. Here, the authors identify seventeen single-nucleotide polymorphisms associated with HRV, lending new insight into the vagal regulation of heart rhythm.
- Ilja M. Nolte
- , M. Loretto Munoz
- & Eco J. C. de Geus
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Article
| Open AccessMeta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism
Endometriosis is a major cause of infertility. Molecular mechanisms underlying the disease involve genetic and environmental risk factors. In a meta-analysis of eleven GWA studies, Sapkota and colleagues identify five novel risk loci, implicating steroid sex hormone pathways in the pathogenesis.
- Yadav Sapkota
- , Valgerdur Steinthorsdottir
- & Dale R. Nyholt
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Article
| Open AccessSequence variant at 8q24.21 associates with sciatica caused by lumbar disc herniation
Lumbar disc herniation (LDH) can cause persistent sciatica, and in some cases surgery is required to relieve symptoms. Here, the authors carry out a genome-wide association study using microdiscectomy as an indicator of severe LDH, and find a locus on chromosome 8 associated with this condition.
- Gyda Bjornsdottir
- , Stefania Benonisdottir
- & Kari Stefansson
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Article
| Open AccessBlunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents
Some adolescents seek novelty, but it is unknown whether the brain circuits underlying this behaviour can be used to predict later, problematic behaviour. Here, authors show that diminished ventral striatal and prefrontal activity in response to anticipated rewards at age 14 in these individuals predicts problematic drug use at age 16.
- Christian Büchel
- , Jan Peters
- & Veronika Ziesch
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Article
| Open AccessIntegrative functional genomics identifies regulatory mechanisms at coronary artery disease loci
Coronary heart disease is the leading cause of death worldwide with multiple environmental and genetic risk factors. Here the authors integrate genomic, epigenomic and transcriptomic mapping to elucidate causal variation and mechanisms of known genetic associations.
- Clint L. Miller
- , Milos Pjanic
- & Thomas Quertermous
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Article
| Open AccessArrhythmia risk stratification of patients after myocardial infarction using personalized heart models
Sudden arrhythmic death is a leading cause of mortality, however approaches to identify at-risk patients are of low sensitivity and specificity. Here, the authors develop a personalized approach to assess arrhythmia risk in post-infarction patients based on cardiac imaging and computational modelling that significantly outperforms existing clinical metrics.
- Hermenegild J. Arevalo
- , Fijoy Vadakkumpadan
- & Natalia A. Trayanova
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Fat, fibre and cancer risk in African Americans and rural Africans
African Americans have much higher colon cancer rates than rural South Africans, which is associated with dietary and metabolic differences. Here, O’Keefe et al.show that switching quantities of fat and fibre leads to reciprocal changes in gut microbiota, metabolites and cancer biomarkers.
- Stephen J. D. O’Keefe
- , Jia V. Li
- & Erwin G. Zoetendal
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Article
| Open AccessNew loci and coding variants confer risk for age-related macular degeneration in East Asians
Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Here, the authors carry out a two-stage genome-wide association study for AMD and identify three new AMD risk loci, highlighting the shared and distinct genetic basis of the disease in East Asians and Europeans.
- Ching-Yu Cheng
- , Kenji Yamashiro
- & Chiea Chuen Khor
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Article |
Smoking exacerbates amyloid pathology in a mouse model of Alzheimer’s disease
A link between smoking and the incidence of Alzheimer’s disease has been implicated in humans. In this study, transgenic mouse models of Alzheimer’s disease exposed to cigarette smoke display increased disease abnormalities in the brain, such as amyloidogenesis, neuroinflammation and tau phosphorylation.
- Ines Moreno-Gonzalez
- , Lisbell D. Estrada
- & Claudio Soto