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This study tests whether hyperperfusion appears even earlier by examining 160 cognitively healthy young adults from the Chinese PREVENT cohort using 3T arterial spin labelling, T1 MRI, and APOE/MAPT rs242557 genotyping.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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is the study aiming to determine about early Alzheimer’s risk?","Question",{"text":62,"@type":63},"The study examines whether cerebral hyperperfusion exists earlier in life among young, cognitively healthy carriers of AD genetic risk factors, focusing on APOE and MAPT variants.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"Which imaging and genetic approaches were used?",{"text":67,"@type":63},"Participants underwent 3T arterial spin labelling and T1 MRI, along with genetic testing for APOE and MAPT rs242557 status.",{"name":69,"@type":60,"acceptedAnswer":70},"What perfusion differences were observed between APOE and MAPT carriers?",{"text":71,"@type":63},"No significant perfusion alterations were seen for APOE genotype, whereas MAPT rs242557 A carriers showed significant hyperperfusion in the left anterior cingulate cortex and left insular 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young adults due to two genetic risk factors of Alzheimer’s disease:  \nAPOE and MAPT  \nSamuel K Bennett 1,*, Jianmin Zeng2,*, Maria-Eleni Dounavi3 , Arshad Majid 1, Sheharyar S Baig 1, Matteo De Marco4,  \nCraig Ritchie5,6, John T O’Brien3 and Li Su 1,3   \nJournal of Cerebral Blood Flow & Metabolism  \n0(0) 1–11  \n! The Author(s) 2025  \nArticle reuse guidelines: [sagepub.com/journals-permissions](sagepub.com/journals-permissions)[ ](sagepub.com/journals-permissions)DOI: 10.1177/0271678X241310731 [journals.sagepub.com/home/jcbfm](journals.sagepub.com/home/jcbfm)  \nAbstract  \nFunctional brain changes such as altered cerebral blood flow occur long before the onset of clinical symptoms in Alzheimer’s disease (AD) and other neurodegenerative disorders. While cerebral hypoperfusion occurs in established AD, middle-aged carriers of genetic risk factors for AD, including APOE e4, display regional hyperperfusion due to hypothesised pleiotropic or compensatory effects, representing a possible early biomarker of AD and facilitating earlier AD diagnosis. However, it is not clear whether hyperperfusion already exists even earlier in life. Here, 160 young and cognitively healthy participants from the Chinese PREVENT cohort underwent 3T arterial spin labelling and T1 MRI and genetic testing for APOE and MAPT rs242557 status. Using FSL, we performed a whole brain voxel-wise analysis and a global mean grey matter analysis comparing for the effects of both risk genes on cerebral perfusion. No significant alterations were seen for APOE genotype, but in MAPTrs242557 A carriers, we observed a significantly hyperperfusion in the left anterior cingulate cortex and left insular cortex. There were no effects of APOE or MAPT status on the global perfusion. These results are novel and may suggest that MAPT genotypes demonstrated a distinct hemodynamic profile in a very young age.  \nKeywords  \nAlzheimer’s disease, arterial spin labelling, cerebral perfusion, functional neuroimaging, genetic risk factors  \nReceived 26 May 2024; Revised 5 November 2024; Accepted 7 December 2024  \nIntroduction  \nAlzheimer’s disease (AD) is the most common cause of dementia globally, 1 and among the most burdensome diseases in older populations, accounting for more disability years in those aged over 60 than stroke, musculoskeletal conditions, cardiovascular disease and all cancers2 and its prevalence is continuing to grow due to ageing populations. AD is heterogeneous in its presentation but it typically presents with progressive memory loss and a combination of other symptoms such as confusion, personality changes and deterioration of speech and vision.1 However, research in recent years has suggested that AD pathogenesis including neuroinflammation and vascular changes start many years before any symptoms occur.3 The two main pathological events leading to AD are the formation of extracellular amyloid beta (Ab) plaques and intracellular  \n1 Sheffield Institute for Translational Neuroscience, Division of Neuroscience, School of Medicine and Population Heath, University of Sheffield, Sheffield, UK  \n2Sino-Britain Centre for Cognition and Ageing Research, Faculty of Psychology, Southwest University, Chongqing, China  \n3Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, UK  \n4Department of Life Sciences, Brunel University London, Uxbridge, UK 5School of Medicine, University of St Andrews, St Andrews, UK 6Scottish Brain Sciences, Edinburgh, UK  \n*These authors contributed equally.  \nCorresponding authors:  \nJianmin Zeng, Sino-Britain Centre for Cognition and Ageing Research, Faculty of Psychology, Southwest University, Chongqing, China.  \nEmail: [james_psych@yeah.net](james_psych@yeah.net)  \nLi Su, Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield, South Yorkshire S10 2HQ, UK.  \nEmail: [l.su@sheffield.ac.uk](l.su@sheffield.a","cbCailLm662N8P4v","https://ap.wps.com/l/cbCailLm662N8P4v","pdf",1024407,11,"English","# Introduction\n## Alzheimer’s disease and genetic risk\n# Methods\n## Participants and cohort\n## Imaging and genetic testing\n# Results\n## APOE effects on cerebral perfusion\n## MAPT rs242557 effects on cerebral perfusion\n## Global perfusion findings\n# Discussion\n## Implications for early biomarkers","[{\"question\":\"What is the study aiming to determine about early Alzheimer’s risk?\",\"answer\":\"The study examines whether cerebral hyperperfusion exists earlier in life among young, cognitively healthy carriers of AD genetic risk factors, focusing on APOE and MAPT variants.\"},{\"question\":\"Which imaging and genetic approaches were used?\",\"answer\":\"Participants underwent 3T arterial spin labelling and T1 MRI, along with genetic testing for APOE and MAPT rs242557 status.\"},{\"question\":\"What perfusion differences were observed between APOE and MAPT carriers?\",\"answer\":\"No significant perfusion alterations were seen for APOE genotype, whereas MAPT rs242557 A carriers showed significant hyperperfusion in the left anterior cingulate cortex and left insular cortex.\"}]","Cerebral perfusion alterations in healthy young adults due to two genetic risk factors of Alzheimer’s disease: APOE and MAPT | PDF",1790685554,28]