{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:42:24Z","timestamp":1790430144397,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,9,7]],"date-time":"2019-09-07T00:00:00Z","timestamp":1567814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001782","name":"University of Melbourne","doi-asserted-by":"publisher","award":["96756"],"award-info":[{"award-number":["96756"]}],"id":[{"id":"10.13039\/501100001782","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Individuals with homozygosity for the apolipoprotein E (<jats:italic>APOE)<\/jats:italic> \u03b54 allele are in the highest risk category for late\u2010onset Alzheimer's disease (LOAD). However, some individuals in this category do not develop LOAD beyond the age of 75 years, despite being at elevated genetic risk. These \u201cresilient\u201d individuals may carry protective genetic factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study aimed to systematically review any previous studies that involved resilient <jats:italic>APOE<\/jats:italic> \u03b54 homozygotes and to identify possible modifying or protective genetic factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifteen studies met our inclusion criteria and reported genetic factors contributing to reduced risk. We found that only two single nucleotide polymorphisms, <jats:italic>CASP7<\/jats:italic> rs10553596 and <jats:italic>SERPINA3<\/jats:italic> rs4934\u2010A\/A, had strong evidence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We found a paucity of studies adequately designed to discover protective genetic factors against LOAD. Many studies combined <jats:italic>APOE<\/jats:italic> \u03b54 homozygotes and heterozygotes together because of small sample sizes and used control populations too young to be clearly defined as controls for LOAD.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.jalz.2019.05.011","type":"journal-article","created":{"date-parts":[[2019,9,7]],"date-time":"2019-09-07T07:14:53Z","timestamp":1567840493000},"page":"1612-1623","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Genetic resilience to Alzheimer's disease in <i>APOE<\/i> \u03b54 homozygotes: A systematic review"],"prefix":"10.1002","volume":"15","author":[{"given":"Aamira J.","family":"Huq","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne VIC Australia"},{"name":"Department of Genomic Medicine Royal Melbourne Hospital Department of Medicine Royal Melbourne Hospital University of Melbourne Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Fransquet","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon M.","family":"Laws","sequence":"additional","affiliation":[{"name":"Collaborative Genomics Group, Centre of Excellence for Alzheimer's Disease Research and Care School of Medical and Health Sciences Edith Cowan University Joondalup Western Australia Australia Australia"},{"name":"School of Pharmacy and Biomedical Sciences Faculty of Health Sciences Curtin Health Innovation Research Institute Curtin University Bentley WA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sebra","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin L.","family":"Masters","sequence":"additional","affiliation":[{"name":"The Florey Institute University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid M.","family":"Winship","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine Royal Melbourne Hospital Department of Medicine Royal Melbourne Hospital University of Melbourne Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"James","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine Royal Melbourne Hospital Department of Medicine Royal Melbourne Hospital University of Melbourne Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Lacaze","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,7]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.06.015"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03550160069041"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60903-8"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-151-4-200908180-00135"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0895-486"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1996.tb32595.x"},{"key":"e_1_2_7_9_2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1186\/s12864-016-2725-z","article-title":"A loss of function variant in CASP7 protects against Alzheimer's disease in homozygous APOE epsilon4 allele carriers","volume":"17","author":"Ayers KL","year":"2016","journal-title":"BMC Genomics"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1159\/000082663"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1665"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2923"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2003.06.008"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-161070"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.12.066"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1998.tb01735.x"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.6.973"},{"key":"e_1_2_7_18_2","first-page":"535","article-title":"Role of genes GSTM1, GSTT1, and MnSOD in the development of late\u2010onset Alzheimer disease and their relationship with APOE 4","volume":"31","author":"Mendonca E","year":"2016","journal-title":"Neurologia"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001308"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160091"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-003-0157-9"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002258"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30053-X"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-018-0273-5"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21699"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000194"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.02.006"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-150993"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.123"},{"key":"e_1_2_7_30_2","doi-asserted-by":"crossref","first-page":"907","DOI":"10.3233\/JAD-131409","article-title":"Risk factors for development of dementia in a unique six\u2010year cohort study. I. An exploratory, pilot study of involvement of the E4 allele of apolipoprotein E, mutations of the hemochromatosis\u2010HFE gene, type 2 diabetes, and stroke","volume":"38","author":"Percy M","year":"2014","journal-title":"J Alzheimers Dis"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1159\/000350368"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2012.10.004"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.01.002"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1159\/000080023"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001584"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1552526019301529?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1552526019301529?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.jalz.2019.05.011","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.jalz.2019.05.011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T23:59:35Z","timestamp":1759881575000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1016\/j.jalz.2019.05.011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,7]]},"references-count":34,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["10.1016\/j.jalz.2019.05.011"],"URL":"https:\/\/doi.org\/10.1016\/j.jalz.2019.05.011","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,7]]},"assertion":[{"value":"2019-09-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}