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We conducted an epigenome-wide association study (EWAS) of a clinically and neuropathologically characterized cohort of 296 brains, including Alzheimer\u2019s disease (AD) and non-demented controls (ND), exploring the relationship with the RNA expression from matched donors. We detected 5246 CpGs and 832 regions differentially methylated, finding overlap with previous EWAS but also new associations. CpGs previously identified in <jats:italic>ANK1, MYOC,<\/jats:italic> and <jats:italic>RHBDF2<\/jats:italic> were differentially methylated, and one of our top hits (<jats:italic>GPR56<\/jats:italic>) was not previously detected. <jats:italic>ANK1<\/jats:italic> was differentially methylated at the region level, along with <jats:italic>APOE<\/jats:italic> and <jats:italic>RHBDF2<\/jats:italic>. Only a small number of genes showed a correlation between DNA methylation and RNA expression statistically significant. Multiblock partial least-squares discriminant analysis showed several CpG sites and RNAs discriminating AD and ND (AUC\u2009=\u20090.908) and strongly correlated with each other. Furthermore, the CpG site cg25038311 was negatively correlated with the expression of 22 genes. Finally, with the functional epigenetic module analysis, we identified a protein\u2013protein network characterized by inverse RNA\/DNA methylation correlation and enriched for \u201cRegulation of insulin-like growth factor transport\u201d, with <jats:italic>IGF1<\/jats:italic> as the hub gene. Our results confirm and extend the previous EWAS, providing new information about a brain region not previously explored in AD DNA methylation studies. The relationship between DNA methylation and gene expression is not significant for most of the genes in our sample, consistently with the complexities in the gene expression regulation.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s10571-022-01307-3","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T17:03:32Z","timestamp":1672765412000},"page":"2289-2307","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Integrated DNA Methylation\/RNA Profiling in Middle Temporal Gyrus of Alzheimer\u2019s Disease"],"prefix":"10.1007","volume":"43","author":[{"given":"Ignazio S.","family":"Piras","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Brokaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinfei","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Weisenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonida","family":"Krate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Delvaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swapna","family":"Mahurkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Blattler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly D.","family":"Siegmund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Sue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geidy E.","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Beach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter W.","family":"Laird","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Huentelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Coleman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,3]]},"reference":[{"key":"1307_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.10.076","author":"BL Adler","year":"2014","unstructured":"Adler BL, Yarchoan M, Hwang HM et al (2014) Neuroprotective effects of the amylin analogue pramlintide on Alzheimer\u2019s disease pathogenesis and cognition. 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