{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T06:26:52Z","timestamp":1785133612739,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Joint Research Fund for Sichuan Province Science and Technology Agency and Southwest Medical University of China","award":["14JC0161"],"award-info":[{"award-number":["14JC0161"]}]},{"name":"Joint Research Fund for Sichuan Province Science and Technology Agency and Southwest Medical University of China","award":["2011204"],"award-info":[{"award-number":["2011204"]}]},{"name":"Joint Research Fund for Sichuan Province Science and Technology Agency and Southwest Medical University of China","award":["2021SYF28"],"award-info":[{"award-number":["2021SYF28"]}]},{"name":"Scientific Research Starting Foundation for Doctors of Southwest Medical University of China","award":["14JC0161"],"award-info":[{"award-number":["14JC0161"]}]},{"name":"Scientific Research Starting Foundation for Doctors of Southwest Medical University of China","award":["2011204"],"award-info":[{"award-number":["2011204"]}]},{"name":"Scientific Research Starting Foundation for Doctors of Southwest Medical University of China","award":["2021SYF28"],"award-info":[{"award-number":["2021SYF28"]}]},{"name":"the Fund for Luzhou Science and Technology Bureau of Sichuan Province of China","award":["14JC0161"],"award-info":[{"award-number":["14JC0161"]}]},{"name":"the Fund for Luzhou Science and Technology Bureau of Sichuan Province of China","award":["2011204"],"award-info":[{"award-number":["2011204"]}]},{"name":"the Fund for Luzhou Science and Technology Bureau of Sichuan Province of China","award":["2021SYF28"],"award-info":[{"award-number":["2021SYF28"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is characterized by progressive cognitive decline and late-stage neurobehavioral issues marked by amyloid-beta plaques and Tau protein tangles. This study aims to investigate Fibulin-1(FBLN1) gene expression in the hippocampal tissue of Presenilin-1\/Presenilin-2 conditional double-knockout (DKO) and double-transgenic (DTG) mice, using single-cell sequencing and experimental methods to verify abnormal methylation status and correlation with AD. Genomic DNA from DKO and DTG mice was used for genotyping. Reduced Representation Bisulfite Sequencing (RRBS) identified 10 genes with abnormal methylation changes, with protein\u2013protein interaction (PPI) analysis highlighting five core genes, including FBLN1. Single-cell sequencing, RT-PCR, and Western blotting (WB) were used to analyze FBLN1 mRNA and protein levels in the hippocampal tissues of early-stage and mid-stage AD DKO, DTG, and CBAC57 mice. RRBS identified 10 genes with abnormal methylation, with PPI highlighting five core genes. Single-cell sequencing showed significant FBLN1 expression in AD groups. RT-PCR and WB indicated elevated FBLN1 mRNA and protein levels in mid-stage AD DKO and DTG mice compared to CBAC57 mice, with no differences in early-stage AD DKO and CBAC57 mice. RRBS revealed hypomethylation of the FBLN1 gene in mid-stage AD DKO mice. Elevated FBLN1 expression in AD models suggests an age-dependent neurodegenerative mechanism independent of amyloid-beta deposition. This study enhances our understanding of AD\u2019s epigenetic mechanisms, which will aid targeted diagnosis, treatment, and prognosis.<\/jats:p>","DOI":"10.3390\/ijms25169036","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T09:13:48Z","timestamp":1724145228000},"page":"9036","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Bioinformatics-Based Study on Methylation Alterations of the FBLN1 Gene in Hippocampal Tissue of Alzheimer\u2019s Disease Model DKO and DTG Mice"],"prefix":"10.3390","volume":"25","author":[{"given":"Rui","family":"Tang","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9868-0959","authenticated-orcid":false,"given":"Yue","family":"Jian","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9665-2609","authenticated-orcid":false,"given":"Zhimin","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5486-8218","authenticated-orcid":false,"given":"Haitao","family":"Wang","sequence":"additional","affiliation":[{"name":"The School of Clinical Medical Sciences, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyu","family":"Miao","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Yang","sequence":"additional","affiliation":[{"name":"The School of Clinical Medical Sciences, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0715-9631","authenticated-orcid":false,"given":"Mingxi","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dugger, B.N., and Dickson, D.W. 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