{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:22:01Z","timestamp":1785216121720,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1A5A2027340"],"award-info":[{"award-number":["NRF-2019R1A5A2027340"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2022R1F1A1063966"],"award-info":[{"award-number":["NRF-2022R1F1A1063966"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2022R1I1A1A01056956"],"award-info":[{"award-number":["2022R1I1A1A01056956"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002642","name":"Korea University","doi-asserted-by":"publisher","award":["O2309441"],"award-info":[{"award-number":["O2309441"]}],"id":[{"id":"10.13039\/501100002642","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Non-alcoholic fatty liver disease (NAFLD) is known to be associated with a high risk of clinically diagnosed Alzheimer\u2019s disease (AD). Additionally, the prevalence of NAFLD and AD is higher in elderly females than in males. However, a sex-specific association between NAFLD and amyloid-beta (A\u03b2) deposition remains unclear. Therefore, we investigated the sex-specific relationship between NAFLD and A\u03b2 deposition in a large-sized cohort of cognitively unimpaired (CU) individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We enrolled 673 (410 [60.9%] females and 263 [39.1%] males) CU individuals aged \u226545\u2009years who underwent A\u03b2 positron emission tomography (PET). The presence of NAFLD, assessed using the hepatic steatosis index, and the severity of NAFLD, assessed using the Fibrosis-4 index, were considered predictors. A\u03b2 deposition on PET was considered as an outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Females had a higher frequency of NAFLD than males (48 and 23.2%, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001). Among females, the presence of NAFLD (\u03b2\u2009=\u20090.216, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001) was predictive of increased A\u03b2 deposition, whereas among males, the presence of NAFLD (\u03b2\u2009=\u20090.191, <jats:italic>p<\/jats:italic>\u2009=\u20090.064) was not associated with A\u03b2 deposition. Among females, the presence of NAFLD with low (\u03b2\u2009=\u20090.254, <jats:italic>p<\/jats:italic>\u2009=\u20090.039), intermediate (\u03b2\u2009=\u20090.201, <jats:italic>p<\/jats:italic>\u2009=\u20090.006), and high fibrosis (\u03b2\u2009=\u20090.257, <jats:italic>p<\/jats:italic>\u2009=\u20090.027) was predictive of increased A\u03b2 deposition. A\u03b2 deposition also increased as the severity of NAFLD increased in females (<jats:italic>p<\/jats:italic> for trend\u2009=\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We highlight the marked influence of NAFLD and its severity on the risk of A\u03b2 deposition in relation to sex. Furthermore, our findings suggest that sex-specific strategies regarding the management of NAFLD are necessary for the prevention of A\u03b2 deposition.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2023.1277392","type":"journal-article","created":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T05:29:53Z","timestamp":1697174993000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Sex-specific relationship between non-alcoholic fatty liver disease and amyloid-\u03b2 in cognitively unimpaired individuals"],"prefix":"10.3389","volume":"15","author":[{"given":"Sung Hoon","family":"Kang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heejin","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo Kyoung","family":"Cheon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Pyo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyemin","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungmi","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-Beom","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duk L.","family":"Na","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoosoo","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Won","family":"Seo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.jalz.2016.03.001","article-title":"2016 Alzheimer's disease facts and figures","volume":"12","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/978-3-319-70178-3_9","article-title":"Sex differences in muscle wasting","volume":"1043","author":"Anderson","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"8489","DOI":"10.1038\/srep08489","article-title":"Neuroinflammation and A\u03b2 accumulation linked to systemic inflammation are decreased by genetic PKR down-regulation","volume":"5","author":"Carret-Rebillat","year":"2015","journal-title":"Sci. Rep."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.1007\/s00259-019-04596-x","article-title":"A new Centiloid method for (18)F-florbetaben and (18)F-flutemetamol PET without conversion to PiB","volume":"47","author":"Cho","year":"2020","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1037\/1040-3590.3.2.168","article-title":"A cognitive battery for dementia: development and measurement characteristics","volume":"3","author":"Christensen","year":"1991","journal-title":"Psychol. Assess. J. Consult. Clin. Psychol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.3390\/nu5051544","article-title":"Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease","volume":"5","author":"Gaggini","year":"2013","journal-title":"Nutrients"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1001\/jama.2017.3090","article-title":"Association between midlife vascular risk factors and estimated brain amyloid deposition","volume":"317","author":"Gottesman","year":"2017","journal-title":"JAMA"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"510","DOI":"10.3350\/cmh.2021.0332","article-title":"Association of non-alcoholic fatty liver disease with incident dementia later in life among elder adults","volume":"28","author":"Jeong","year":"2022","journal-title":"Clin. Mol. Hepatol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"924550","DOI":"10.3389\/fnagi.2022.924550","article-title":"Independent effect of body mass index variation on amyloid-\u03b2 positivity","volume":"14","author":"Kang","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"102685","DOI":"10.1016\/j.nicl.2021.102685","article-title":"Cortical neuroanatomical changes related to specific neuropsychological deficits in subcortical vascular cognitive impairment","volume":"30","author":"Kang","year":"2021","journal-title":"NeuroImage Clin."},{"key":"ref11","first-page":"27","article-title":"Protein-protein interaction analysis of Alzheimer\u2019s disease and NAFLD based on systems biology methods unhide common ancestor pathways","volume":"11","author":"Karbalaei","year":"2018","journal-title":"Gastroenterol. Hepatol, Bed Bench"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"360","DOI":"10.22037\/ghfbb.v15i4.2480","article-title":"Comparison of hepatic steatosis index as noninvasive diagnostic tool and liver ultrasound for non-alcoholic steatosis in the adult population","volume":"15","author":"Khani","year":"2022","journal-title":"Gastroenterol. Hepatol, Bed Bench"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12974-015-0467-5","article-title":"Non-alcoholic fatty liver disease induces signs of Alzheimer's disease (AD) in wild-type mice and accelerates pathological signs of AD in an AD model","volume":"13","author":"Kim","year":"2016","journal-title":"J. Neuroinflammation"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e1045","DOI":"10.1212\/wnl.0000000000008084","article-title":"Sex-specific relationship of cardiometabolic syndrome with lower cortical thickness","volume":"93","author":"Kim","year":"2019","journal-title":"Neurology"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1111\/liv.15244","article-title":"Association between non-alcoholic fatty liver disease and the risk of dementia: a nationwide cohort study","volume":"42","author":"Kim","year":"2022","journal-title":"Liver Int."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/1742-2094-9-151","article-title":"Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice","volume":"9","author":"Krstic","year":"2012","journal-title":"J. Neuroinflammation"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.dld.2009.08.002","article-title":"Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease","volume":"42","author":"Lee","year":"2010","journal-title":"Digest. Liver Dis."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.3233\/jad-170537","article-title":"Trajectories of physiological brain aging and related factors in people aged from 20 to over-80","volume":"65","author":"Lee","year":"2018","journal-title":"J. Alzheimer's Dis."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1111\/liv.14669","article-title":"Prognostic accuracy of FIB-4, NAFLD fibrosis score and APRI for NAFLD-related events: a systematic review","volume":"41","author":"Lee","year":"2021","journal-title":"Liver Int."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1002\/hep.30626","article-title":"Sex differences in nonalcoholic fatty liver disease: state of the art and identification of research gaps","volume":"70","author":"Lonardo","year":"2019","journal-title":"Hepatology"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.bbi.2015.08.020","article-title":"Estrogen protects the blood-brain barrier from inflammation-induced disruption and increased lymphocyte trafficking","volume":"51","author":"Maggioli","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1111\/j.1365-2265.2006.02543.x","article-title":"Effects of HRT on liver enzyme levels in women with type 2 diabetes: a randomized placebo-controlled trial","volume":"65","author":"McKenzie","year":"2006","journal-title":"Clin. Endocrinol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1038\/ajg.2014.155","article-title":"Development, external validation, and comparative assessment of a new diagnostic score for hepatic steatosis","volume":"109","author":"Meffert","year":"2014","journal-title":"Am. J. Gastroenterol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1186\/s12974-020-01876-4","article-title":"Lipocalin 2 induces neuroinflammation and blood-brain barrier dysfunction through liver-brain axis in murine model of nonalcoholic steatohepatitis","volume":"17","author":"Mondal","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.bbrc.2007.05.158","article-title":"Estrogen has anti-amyloidogenic effects on Alzheimer's beta-amyloid fibrils in vitro","volume":"359","author":"Morinaga","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"132","DOI":"10.3390\/diagnostics11010132","article-title":"Prediction of nonalcoholic fatty liver disease using noninvasive and non-imaging procedures in Japanese health checkup examinees","volume":"11","author":"Murayama","year":"2021","journal-title":"Diagnostics"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1001\/jamaneurol.2013.5390","article-title":"Associations between serum cholesterol levels and cerebral amyloidosis","volume":"71","author":"Reed","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.yfrne.2013.08.001","article-title":"Estrogen: a master regulator of bioenergetic systems in the brain and body","volume":"35","author":"Rettberg","year":"2014","journal-title":"Front. Neuroendocrinol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.dld.2020.10.014","article-title":"Liver fibrosis marker is an independent predictor of cardiovascular morbidity and mortality in the general population","volume":"53","author":"Schonmann","year":"2021","journal-title":"Digest. Liver Dis."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"3510","DOI":"10.1073\/pnas.1112209109","article-title":"Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver","volume":"109","author":"Sehgal","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1212\/wnl.0000000000002498","article-title":"Nonalcoholic fatty liver disease is associated with cognitive function in adults","volume":"86","author":"Seo","year":"2016","journal-title":"Neurology"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"100218","DOI":"10.1016\/j.jhepr.2020.100218","article-title":"Non-alcoholic fatty liver disease does not increase dementia risk although histology data might improve risk prediction","volume":"3","author":"Shang","year":"2021","journal-title":"JHEP Rep."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3988\/jcn.2011.7.2.60","article-title":"Biomarkers predicting Alzheimer's disease in cognitively Normal aging","volume":"7","author":"Shim","year":"2011","journal-title":"J. Clin. Neurol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e12065","DOI":"10.1002\/trc2.12065","article-title":"Liver fibrosis score, physical frailty, and the risk of dementia in older adults: the Italian longitudinal study on aging","volume":"6","author":"Solfrizzi","year":"2020","journal-title":"Alzheimers Dement."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1001\/jamaneurol.2020.0387","article-title":"Association of Factors with Elevated Amyloid Burden in clinically Normal older individuals","volume":"77","author":"Sperling","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1124\/mol.107.036913","article-title":"Insulin facilitates the hepatic clearance of plasma amyloid beta-peptide (1 40) by intracellular translocation of low-density lipoprotein receptor-related protein 1 (LRP-1) to the plasma membrane in hepatocytes","volume":"72","author":"Tamaki","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"537","DOI":"10.5009\/gnl19236","article-title":"Characteristic features of nonalcoholic fatty liver disease in Japan with a focus on the roles of age, sex and body mass index","volume":"14","author":"Tobari","year":"2020","journal-title":"Gut Liver"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1002\/hep.29113","article-title":"Liver fibrosis scores predict liver disease mortality in the United States population","volume":"66","author":"Unalp-Arida","year":"2017","journal-title":"Hepatology"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1111\/liv.14161","article-title":"Non-alcoholic fatty liver disease, liver fibrosis score and cognitive function in middle-aged adults: the Framingham study","volume":"39","author":"Weinstein","year":"2019","journal-title":"Liver Int."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.jalz.2014.03.011","article-title":"Insulin resistance predicts brain amyloid deposition in late middle-aged adults","volume":"11","author":"Willette","year":"2015","journal-title":"Alzheimers Dement."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2023.1277392\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T05:30:02Z","timestamp":1697175002000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2023.1277392\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,13]]},"references-count":41,"alternative-id":["10.3389\/fnagi.2023.1277392"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2023.1277392","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,13]]},"article-number":"1277392"}}