{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T12:16:15Z","timestamp":1778501775729,"version":"3.51.4"},"update-to":[{"DOI":"10.12688\/f1000research.18671.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000}}],"reference-count":59,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    The\n                    <ns4:italic>APOE<\/ns4:italic>\n                    gene encodes apolipoprotein \u03b5 (ApoE), a protein that associates with lipids to form lipoproteins that package and traffic cholesterol and lipids through the bloodstream. There are at least three different alleles of the\n                    <ns4:italic>APOE<\/ns4:italic>\n                    gene:\n                    <ns4:italic>APOE2<\/ns4:italic>\n                    ,\n                    <ns4:italic>APOE3<\/ns4:italic>\n                    , and\n                    <ns4:italic>APOE4<\/ns4:italic>\n                    . The\n                    <ns4:italic>APOE4<\/ns4:italic>\n                    allele increases an individual's risk for developing late-onset Alzheimer disease (AD) in a dose-dependent manner. Sex differences have been reported for AD susceptibility, age of onset, and symptom progression, with females being more affected than males.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    In this study, we use a systems biology approach to examine gene expression patterns in the brains of aged female and male individuals who are positive for the\n                    <ns4:italic>APOE4<\/ns4:italic>\n                    allele in order to identify possible sex-related differences that may be relevant to AD.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    Based on correlation analysis, we identified a large number of genes with an expression pattern similar to that of\n                    <ns4:italic>APOE<\/ns4:italic>\n                    in\n                    <ns4:italic>APOE4<\/ns4:italic>\n                    -positive individuals. The number of these genes was much higher in\n                    <ns4:italic>APOE4<\/ns4:italic>\n                    -positive females than in\n                    <ns4:italic>APOE4<\/ns4:italic>\n                    -positive males, who in turn had more of such genes than\n                    <ns4:italic>APOE4<\/ns4:italic>\n                    -negative control groups. Our findings also indicate a significant sex* genotype interaction for the CNTNAP2 gene, a member of the neurexin family and a significant interaction for brain area*sex* genotype for PSEN2, a risk factor gene for AD.\u00a0\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    Profiling of these genes using Gene Ontology (GO) term classification, pathway enrichment, and differential expression analysis supports the idea of a transcriptional role of\n                    <ns4:italic>APOE<\/ns4:italic>\n                    with respect to sex differences and AD.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.18671.2","type":"journal-article","created":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T11:10:10Z","timestamp":1563880210000},"page":"387","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Sex differences in gene expression patterns associated with the APOE4 allele"],"prefix":"10.12688","volume":"8","author":[{"given":"Michelle","family":"Hsu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehek","family":"Dedhia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6638-202X","authenticated-orcid":false,"given":"Wim E","family":"Crusio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6134-2560","authenticated-orcid":false,"given":"Anna","family":"Delprato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2019,7,23]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"563-573","DOI":"10.1002\/ana.24135","article-title":"Sex modifies the APOE-related risk of developing Alzheimer disease.","volume":"75","author":"A Altmann","year":"2014","journal-title":"Ann Neurol."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"157-165","DOI":"10.1385\/JMN:23:3:157","article-title":"APOE genotype effects on Alzheimer's disease onset and epidemiology.","volume":"23","author":"J Ashford","year":"2004","journal-title":"J Mol Neurosci."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"1464-1471","DOI":"10.1212\/WNL.0b013e3182553c48","article-title":"Genotype patterns at PICALM, CR1, BIN1, CLU, and APOE genes are associated with episodic memory.","volume":"78","author":"S Barral","year":"2012","journal-title":"Neurology."},{"key":"ref-70","doi-asserted-by":"publisher","first-page":"1163-72","DOI":"10.2147\/CIA.S85808","article-title":"Mutations in presenilin 2 and its implications in Alzheimer's disease and other dementia-associated disorders.","volume":"10","author":"Y Cai","year":"2015","journal-title":"Clin Interv Aging."},{"key":"ref-4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092603","article-title":"Heat Shock Proteins in Alzheimer's Disease: Role and Targeting.","volume":"19","author":"C Campanella","year":"2018","journal-title":"Int J Mol Sci."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"921-923","DOI":"10.1126\/science.8346443","article-title":"Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.","volume":"261","author":"E Corder","year":"1993","journal-title":"Science."},{"key":"ref-5","doi-asserted-by":"crossref","first-page":"505-530","DOI":"10.2217\/17460875.3.5.505","article-title":"Apolipoprotein E and cholesterol in aging and disease in the brain.","volume":"3","author":"E de Chaves","year":"2008","journal-title":"Future Lipidol."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1038\/418932a","article-title":"Cognitive change and the APOE epsilon 4 allele.","volume":"418","author":"I Deary","year":"2002","journal-title":"Nature."},{"key":"ref-8","article-title":"Workbook 1. Positive and negative gene correlates for APOE4+ and APOE4- females. Frontal white matter, Hippocampus, Parietal cortex, and Temporal cortex","author":"A Delprato","year":"2019a","journal-title":"figshare."},{"key":"ref-9","article-title":"Workbook 2. Positive and negative gene correlates for APOE4+ and APOE4- males. Frontal white matter, Hippocampus, Parietal cortex, and Temporal cortex.","author":"A Delprato","year":"2019b","journal-title":"figshare."},{"key":"ref-10","article-title":"Workbook 3. Common and unique genes for APOE4+ and APOE4- males and females. Frontal white matter, Hippocampus, Parietal cortex, Temporal cortex.","author":"A Delprato","year":"2019c","journal-title":"figshare."},{"key":"ref-11","article-title":"Workbook 4. Keywords for gene correlates APOE4+ and APOE4- females and males. Frontal white matter, Hippocampus, Parietal cortex, Temporal cortex.","author":"A Delprato","year":"2019d","journal-title":"figshare."},{"key":"ref-12","article-title":"Workbook 5. KEGG Pathways for positive and negative correlates associated with APOE4+ females and males. Frontal white matter, Hippocampus, Parietal cortex, Temporal cortex.","author":"A Delprato","year":"2019e","journal-title":"figshare."},{"key":"ref-13","article-title":"Workbook 6. Differential gene expression in APOE4+ and APOE4- females and males. Frontal white matter, Hippocampus, Parietal cortex, Temporal cortex.","author":"A Delprato","year":"2019f","journal-title":"figshare."},{"key":"ref-14","article-title":"Workbook 7. Differentially expressed transcription factors in females and males.GO Biological Process. Frontal white matter, Hippocampus, Parietal cortex, Temporal cortex.","author":"A Delprato","year":"2019g","journal-title":"figshare."},{"key":"ref-52","article-title":"Workbook 8. CNTNAP2 gene expression and correlation analysis for APOE4-positive and APOE4-negative females and males. 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Frontal white matter, Hippocampus, Parietal cortex, Temporal cortex.","author":"A Delprato","year":"2019k","journal-title":"figshare."},{"key":"ref-56","article-title":"Workbook 12. APP gene expression and correlation analysis for APOE4-positive and APOE4-negative females and males. Frontal white matter, Hippocampus, Parietal cortex, Temporal cortex.","author":"A Delprato","year":"2019l","journal-title":"figshare."},{"key":"ref-57","article-title":"Workbook 13. ADAM 10 gene expression and correlation analysis for APOE4-positive and APOE4-negative females and males. Frontal white matter, Hippocampus, Parietal cortex, Temporal cortex.","author":"A Delprato","year":"2019m","journal-title":"figshare."},{"key":"ref-58","article-title":"Workbook 14. TREM2 gene expression and correlation analysis for APOE4-positive and APOE4-negative females and males. Frontal white matter, Hippocampus, Parietal cortex, Temporal cortex.","author":"A Delprato","year":"2019n","journal-title":"figshare."},{"key":"ref-59","article-title":"Extended data Figure 1. Gene expression graphs for CNTNAP2 in APOE4-positive and APOE4- negative females and males. Frontal white matter, Hippocampus, Parietal cortex, Temporal cortex.","author":"A Delprato","year":"2019o","journal-title":"figshare."},{"key":"ref-60","article-title":"Extended data Figure 2. Gene expression graphs for PSEN2 in APOE4-positive and APOE4- negative females and males. Frontal white matter, Hippocampus, Parietal cortex, Temporal cortex.","author":"A Delprato","year":"2019p","journal-title":"figshare."},{"key":"ref-61","article-title":"Extended data Figure 3. Gene expression graphs for APOE in APOE4-positive and APOE4- negative females and males. 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