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Self-antigen with strong-binding affinity is considered to be pathogenic. We aim to investigate whether strong-binding affinity self-antigen load is associated with early\/late-onset Alzheimer\u2019s disease (AD). A total of 54 AD samples (22 early-onset, 32 late-onset) underwent next-generation sequencing (NGS) for whole-exome sequencing. Genotypes of HLA class I genes and germline mutations were obtained for estimation of the binding affinity and number of self-antigens. For each patient, self-antigen load was estimated by adding up the number of self-antigens with strong-binding affinity. Self-antigen load of early-onset AD was significantly higher than late-onset AD (mean\u2009\u00b1\u2009SD: 6115\u2009\u00b1\u20092430 vs 4373\u2009\u00b1\u20092492;<jats:italic>p<\/jats:italic>\u2009=\u20090.011). An appropriate cutoff value 2503 for dichotomizing self-antigen load was obtained by receiver operating characteristic (ROC) curve analysis. Patients were then dichotomized into high or low self-antigen load groups in the binary multivariate logistic regression analysis. Adjusted odds ratio of the high self-antigen load (&gt;2503) was 14.22 (95% CI, 1.22\u2013165.70;<jats:italic>p<\/jats:italic>\u2009=\u20090.034) after controlling other covariates including gender, education, ApoE status, and baseline CDR score. This is the first study using NGS to investigate germline mutations generated self-antigen load in AD. As strong-binding affinity self-antigen is considered to be pathogenic in neuroinflammation, our finding indicated that self-antigen load did have a role in the pathogenesis of AD owing to its association with neuroinflammation. This finding may also contribute to further research regarding disease mechanism and development of novel biomarkers or treatment.<\/jats:p>","DOI":"10.1038\/s41398-020-0826-6","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T18:03:45Z","timestamp":1589306625000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Association of early-onset Alzheimer\u2019s disease with germline-generated high affinity self-antigen load"],"prefix":"10.1038","volume":"10","author":[{"given":"Poyin","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Han","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Hsuan","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Ling","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Chuan","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiou-Lian","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Kuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsuan-Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,12]]},"reference":[{"key":"826_CR1","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.biopsych.2014.05.006","volume":"77","author":"CM Karch","year":"2015","unstructured":"Karch, C. 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