{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T19:11:29Z","timestamp":1784056289977,"version":"3.55.0"},"update-to":[{"DOI":"10.12688\/f1000research.27096.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000}}],"reference-count":61,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p><ns4:bold>Background:<\/ns4:bold>People with Down Syndrome (DS) are born with an extra copy of Chromosome (Chr) 21 and many of these individuals develop Alzheimer\u2019s Disease (AD) when they age. This is due at least in part to the extra copy of the APP gene located on Chr 21. By 40 years, most people with DS have amyloid plaques which disrupt brain cell function and increase their risk for AD. About half of the people with DS develop AD and the associated dementia around 50 to 60 years of age, which is about the age at which the hereditary form of AD, early onset AD, manifests. In the absence of Chr 21 trisomy, duplication of APP alone is a cause of early onset Alzheimer\u2019s disease, making it likely that having three copies of APP is important in the development of AD and in DS.<\/ns4:p><ns4:p><ns4:bold>Methods:<\/ns4:bold>We investigate the relationship between AD and DS through integrative analysis of genesets derived from a MeSH query of AD and DS associated beta amyloid peptides, Chr 21, GWAS identified AD risk factor genes, and differentially expressed genes in individuals with DS.<\/ns4:p><ns4:p><ns4:bold>Results:<\/ns4:bold>\u00a0Unique and shared aspects of each geneset were evaluated based on \u00a0functional enrichment analysis, transcription factor profile and network interactions. Genes that may be important to both disorders in the context of direct association with APP processing, Tau post translational modification \u00a0and network connectivity are ACSM1, APBA2, APLP1, BACE2, BCL2L, COL18A1, DYRK1A, IK, KLK6, METTL2B, MTOR, NFE2L2, NFKB1, PRSS1, QTRT1, RCAN1, RUNX1, SAP18 SOD1, SYNJ1, S100B.<\/ns4:p><ns4:p><ns4:bold>Conclusions:<\/ns4:bold>Our findings confirm that oxidative stress, apoptosis, inflammation and immune system processes likely contribute to the pathogenesis of AD and DS which is consistent with other published reports.<\/ns4:p>","DOI":"10.12688\/f1000research.27096.2","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T13:40:06Z","timestamp":1635169206000},"page":"1299","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Common genetic signatures of Alzheimer\u2019s disease in Down 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syndrome.","volume":"12","author":"T Annus","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"305-11","DOI":"10.1111\/jnc.12202","article-title":"Alzheimer's A\u03b242 and A\u03b240 peptides form interlaced amyloid fibrils.","volume":"126","author":"L Gu","year":"2013","journal-title":"J Neurochem."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"813-21","DOI":"10.1046\/j.1460-9568.2003.02506.x","article-title":"Beta-amyloid peptide potentiates inflammatory responses induced by lipopolysaccharide, interferon -gamma and \u2018advanced glycation endproducts\u2019 in a murine microglia cell line.","volume":"17","author":"J Gasic-Milenkovic","year":"2003","journal-title":"Eur J Neurosci."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"213-27","DOI":"10.1177\/0891988710383571","article-title":"Genetics of Alzheimer disease.","volume":"23","author":"L Bekris","year":"2010","journal-title":"J Geriatr 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Genet."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"2977-83","DOI":"10.1093\/brain\/awl203","article-title":"APP duplication is sufficient to cause early onset Alzheimer\u2019s dementia with cerebral amyloid angiopathy.","volume":"129","author":"K Sleegers","year":"2006","journal-title":"Brain."},{"key":"ref-17","doi-asserted-by":"crossref","first-page":"445-54","DOI":"10.31887\/DCNS.2013.15.4\/hjahn","article-title":"Memory loss in Alzheimer\u2019s disease.","volume":"15","author":"H Jahn","year":"2013","journal-title":"Dialogues Clin Neurosci."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"927804","DOI":"10.1155\/2014\/927804","article-title":"Behavioral and psychological symptoms in Alzheimer\u2019s disease.","volume":"2014","author":"X Li","year":"2014","journal-title":"Biomed Res Int."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"233-44","DOI":"10.1111\/1469-7610.00604","article-title":"Verbal short-term memory deficits in Down 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Keyword Gene Enrichment: Enrichment of the AD-DS, Chr 21, AD risk factors, DEX DFC and CBC genesets.","author":"A Delprato","year":"2020","journal-title":"figshare."},{"key":"ref-42","article-title":"Extended Data Workbook 4. GO Terms and Pathways: Gene Ontology Biological Process terms and pathways associated with the AD-DS and Chr 21 genesets.","author":"A Delprato","year":"2020","journal-title":"figshare."},{"key":"ref-43","article-title":"Extended Data Workbook 5. Transcription Factors: TFs present in the AD-DS, Chr 21 genesets.","author":"A Delprato","year":"2020","journal-title":"figshare."},{"key":"ref-44","doi-asserted-by":"publisher","first-page":"706-14","DOI":"10.1002\/jbmr.2379","article-title":"Cbfb regulates bone development by stabilizing Runx family proteins.","volume":"30","author":"X Qin","year":"2015","journal-title":"J Bone Miner Res."},{"key":"ref-45","doi-asserted-by":"publisher","first-page":"103-16","DOI":"10.1007\/978-981-10-3233-2_8","article-title":"Roles of Runx Genes in Nervous System Development.","volume":"962","author":"J Wang","year":"2017","journal-title":"Adv Exp Med Biol."},{"key":"ref-46","doi-asserted-by":"publisher","first-page":"144-8","DOI":"10.1016\/j.neulet.2010.10.010","article-title":"Association of variants within APOE, SORL1, RUNX1, BACE1 and ALDH18A1 with dementia in Alzheimer's disease in subjects with Down syndrome.","volume":"487","author":"A Patel","year":"2011","journal-title":"Neurosci Lett."},{"key":"ref-47","doi-asserted-by":"publisher","first-page":"a020461","DOI":"10.1101\/cshperspect.a020461","article-title":"Transcriptional and Epigenetic Regulation of Oligodendrocyte Development and Myelination in the Central Nervous System.","volume":"7","author":"B Emery","year":"2015","journal-title":"Cold Spring Harb Perspect Biol."},{"key":"ref-48","doi-asserted-by":"publisher","first-page":"927-34","DOI":"10.1038\/nn.2600","article-title":"Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome.","volume":"13","author":"L Chakrabarti","year":"2010","journal-title":"Nat Neurosci."},{"key":"ref-49","doi-asserted-by":"publisher","first-page":"54-9","DOI":"10.1016\/j.neulet.2009.05.051","article-title":"Evidence that variation in the oligodendrocyte lineage transcription factor 2 (OLIG2) gene is associated with psychosis in Alzheimer's disease.","volume":"461","author":"R Sims","year":"2009","journal-title":"Neurosci 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deficiency replicates transcriptomic changes in Alzheimer's patients and worsens APP and TAU pathology.","volume":"13","author":"A Rojo","year":"2017","journal-title":"Redox Biol."},{"key":"ref-54","doi-asserted-by":"publisher","first-page":"12516-23","DOI":"10.1073\/pnas.1819541116","article-title":"NRF2\/ARE pathway negatively regulates BACE1 expression and ameliorates cognitive deficits in mouse Alzheimer's models.","volume":"116","author":"G Bahn","year":"2019","journal-title":"Proc Natl Acad Sci USA."},{"key":"ref-55","doi-asserted-by":"publisher","first-page":"120-35","DOI":"10.1007\/s12035-013-8505-8","article-title":"Targeting the mTOR signaling network for Alzheimer's disease therapy.","volume":"49","author":"C Wang","year":"2014","journal-title":"Mol Neurobiol."},{"key":"ref-56","doi-asserted-by":"publisher","first-page":"1015-30","DOI":"10.2147\/NDT.S75717","article-title":"Activation of mTOR: a culprit of Alzheimer's disease?","volume":"11","author":"Z Cai","year":"2015","journal-title":"Neuropsychiatr Dis Treat."},{"key":"ref-57","doi-asserted-by":"publisher","first-page":"15556-70","DOI":"10.1074\/jbc.M112.435123","article-title":"Mammalian target of rapamycin (mTor) mediates tau protein dyshomeostasis: implication for Alzheimer disease.","volume":"288","author":"Z Tang","year":"2013","journal-title":"J Biol Chem."},{"key":"ref-58","doi-asserted-by":"publisher","first-page":"809-21","DOI":"10.3233\/JAD-2009-0976","article-title":"Inflammation and NF-kappaB in Alzheimer's disease and diabetes.","volume":"16","author":"I Granic","year":"2009","journal-title":"J Alzheimers Dis."},{"key":"ref-59","doi-asserted-by":"publisher","first-page":"17-20","DOI":"10.1016\/s0304-3940(97)00797-0","article-title":"Alteration of transcription factors NF-kappaB and STAT1 in Alzheimer's disease brains.","volume":"237","author":"Y Kitamura","year":"1997","journal-title":"Neurosci 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