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To explore whether the <jats:italic>BIN1<\/jats:italic> methylation in peripheral blood changed in the early stage of LOAD, we included 814 participants (484 cognitively normal participants [CN] and 330 participants with subjective cognitive decline [SCD]) from the Chinese Alzheimer\u2019s Biomarker and LifestylE (CABLE) database. Then we tested associations of methylation of <jats:italic>BIN1<\/jats:italic> promoter in peripheral blood with the susceptibility for preclinical AD or early changes of cerebrospinal fluid (CSF) AD-related biomarkers. Results showed that SCD participants with significant AD biological characteristics had lower methylation levels of <jats:italic>BIN1<\/jats:italic> promoter, even after correcting for covariates. Hypomethylation of <jats:italic>BIN1<\/jats:italic> promoter were associated with decreased CSF A\u03b242 (<jats:italic>p<\/jats:italic>\u2009=\u20090.0008), as well as increased p-tau\/A\u03b242 (<jats:italic>p<\/jats:italic>\u2009=\u20090.0001) and t-tau\/A\u03b242 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) in total participants. Subgroup analysis showed that the above associations only remained in the SCD subgroup. In addition, hypomethylation of <jats:italic>BIN1<\/jats:italic> promoter was also accompanied by increased CSF p-tau (<jats:italic>p<\/jats:italic>\u2009=\u20090.0028) and t-tau (<jats:italic>p<\/jats:italic>\u2009=\u20090.0130) in the SCD subgroup, which was independent of CSF A\u03b242. Finally, above associations were still significant after correcting single nucleotide polymorphic sites (SNPs) and interaction of <jats:italic>APOE<\/jats:italic> \u025b4 status. Our study is the first to find a robust association between hypomethylation of <jats:italic>BIN1<\/jats:italic> promoter in peripheral blood and preclinical AD. This provides new evidence for the involvement of <jats:italic>BIN1<\/jats:italic> in AD, and may contribute to the discovery of new therapeutic targets for AD.<\/jats:p>","DOI":"10.1038\/s41398-021-01218-9","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T15:12:06Z","timestamp":1612278726000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Association between methylation of BIN1 promoter in peripheral blood and preclinical Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"11","author":[{"given":"Hao","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Lin","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Ning","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-He","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Hui","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2532-383X","authenticated-orcid":false,"given":"Jin-Tai","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"key":"1218_CR1","doi-asserted-by":"publisher","first-page":"M117","DOI":"10.1093\/gerona\/52A.2.M117","volume":"52","author":"M Gatz","year":"1997","unstructured":"Gatz, M. et al. 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