{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:47:06Z","timestamp":1770749226536,"version":"3.50.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T00:00:00Z","timestamp":1506297600000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/academic.oup.com\/journals\/pages\/about_us\/legal\/notices"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03-AG048077"],"award-info":[{"award-number":["R03-AG048077"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08-AG049938"],"award-info":[{"award-number":["K08-AG049938"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>In an effort to better understand the molecular drivers of synaptic and neurophysiologic dysfunction in Alzheimer\u2019s disease (AD), we analyzed neuronal gene expression data from human AD brain tissue to identify master regulators of synaptic gene expression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Master regulator analysis identifies ZCCHC17 as normally supporting the expression of a network of synaptic genes, and predicts that ZCCHC17 dysfunction in AD leads to lower expression of these genes. We demonstrate that ZCCHC17 is normally expressed in neurons and is reduced early in the course of AD pathology. We show that ZCCHC17 loss in rat neurons leads to lower expression of the majority of the predicted synaptic targets and that ZCCHC17 drives the expression of a similar gene network in humans and rats. These findings support a conserved function for ZCCHC17 between species and identify ZCCHC17 loss as an important early driver of lower synaptic gene expression in AD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Matlab and R scripts used in this paper are available at https:\/\/github.com\/afteich\/AD_ZCC<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btx608","type":"journal-article","created":{"date-parts":[[2017,9,22]],"date-time":"2017-09-22T19:12:56Z","timestamp":1506107576000},"page":"367-371","source":"Crossref","is-referenced-by-count":17,"title":["ZCCHC17 is a master regulator of synaptic gene expression in Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"34","author":[{"given":"Zeljko","family":"Tomljanovic","sequence":"first","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University, New York, NY, USA"},{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Columbia University, New York, NY, USA"}]},{"given":"Mitesh","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University, New York, NY, USA"},{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Columbia University, New York, NY, USA"}]},{"given":"William","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Columbia University, New York, NY, USA"}]},{"given":"Andrea","family":"Califano","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Columbia University, New York, NY, USA"}]},{"given":"Andrew F","family":"Teich","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University, New York, NY, USA"},{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Columbia University, New York, NY, USA"}]}],"member":"286","published-online":{"date-parts":[[2017,9,22]]},"reference":[{"key":"2023012712282939100_btx608-B1","doi-asserted-by":"crossref","first-page":"e0120352","DOI":"10.1371\/journal.pone.0120352","article-title":"Assembly and interrogation of Alzheimer's disease genetic networks reveal novel regulators of progression","volume":"10","author":"Aubry","year":"2015","journal-title":"PLoS One"},{"key":"2023012712282939100_btx608-B2","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/ng1532","article-title":"Reverse engineering of regulatory networks in human B cells","volume":"37","author":"Basso","year":"2005","journal-title":"Nat. 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