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Targeting neuroplasticity, cardiovascular, and cognitive-associated : Genomic variants in familial alzheimer’s disease

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dc.creatorVélez, Jorge I.
dc.creatorLopera, Francisco
dc.creatorCreagh, Penelope K.
dc.creatorPiñeros, Laura B.
dc.creatorDas, Debjani
dc.creatorCervantes-Henríquez, Martha L.
dc.creatorAcosta-López, Johan E.
dc.creatorIsaza-Ruget, Mario A.
dc.creatorEspinosa, Lady G.
dc.creatorEasteal, Simon
dc.creatorQuintero Hernández, Gustavo Adolfo
dc.creatorTamar Silva, Claudia
dc.creatorMastronardi, Claudio
dc.creatorArcos-Burgos, Mauricio
dc.creator.googleVélez, Jorge I.
dc.creator.googleLopera, Francisco
dc.creator.googleCreagh, Penelope K.
dc.creator.googlePiñeros, Laura B.
dc.creator.googleDas, Debjani
dc.creator.googleCervantes-Henríquez, Martha L.
dc.creator.googleAcosta-López, Johan E.
dc.creator.googleIsaza-Ruget, Mario A.
dc.creator.googleEspinosa, Lady G.
dc.creator.googleEasteal, Simon
dc.creator.googleQuintero, Gustavo A.
dc.creator.googleTamar Silva, Claudia
dc.creator.googleMastronardi, Claudio A.
dc.creator.googleArcos-Burgos, Mauricio
dc.date.accessioned2019-02-20T20:14:29Z
dc.date.available2019-02-20T20:14:29Z
dc.date.created2018
dc.date.issued2018
dc.description.abstractThe identification of novel genetic variants contributing to the widespread in the age of onset (AOO) of Alzheimer’s disease (AD) could aid in the prognosis and/or development of new therapeutic strategies focused on early interventions. We recruited 78 individuals with AD from the Paisa genetic isolate in Antioquia, Colombia. These individuals belong to the world largest multigenerational and extended pedigree segregating AD as a consequence of a dominant fully penetrant mutation in the PSEN1 gene and exhibit an AOO ranging from the early 1930s to the late 1970s. To shed light on the genetic underpinning that could explain the large spread of the age of onset (AOO) of AD, 64 single nucleotide polymorphisms (SNP) associated with neuroanatomical, cardiovascular, and cognitive measures in AD were genotyped. Standard quality control and filtering procedures were applied, and single- and multi-locus linear mixed-effects models were used to identify AOO-associated SNPs. A full two-locus interaction model was fitted to define how identified SNPs interact to modulate AOO. We identified two key epistatic interactions between the APOE*E2 allele and SNPs ASTN2-rs7852878 and SNTG1-rs16914781 that delay AOO by up to ~ 8 years (95% CI 3.2–12.7, P = 1.83 × 10−3) and ~ 7.6 years (95% CI 3.3–11.8, P = 8.69 × 10−4), respectively, and validated our previous finding indicating that APOE*E2 delays AOO of AD in PSEN1 E280 mutation carriers. This new evidence involving APOE*E2 as an AOO delayer could be used for developing precision medicine approaches and predictive genomics models to potentially determine AOO in individuals genetically predisposed to AD. © 2018, The Author(s).eng
dc.format.mimetypeapplication/pdf
dc.identifier.doi10.1007/s12035-018-1298-z
dc.identifier.issn0893-7648
dc.identifier.urihttp://repository.urosario.edu.co/handle/10336/19120
dc.language.isoengspa
dc.relation.citationTitleMolecular Neurobiology
dc.relation.ispartofMolecular Neurobiology, ISSN:8937-648, Vol. (2018)spa
dc.relation.urihttps://link.springer.com/article/10.1007%2Fs12035-018-1298-zspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.bibliographicCitationBrookmeyer, R., Johnson, E., Ziegler-Graham, K., Arrighi, H.M., Forecasting the global burden of Alzheimer’s disease (2007) Alzheimers Dement, 3 (3), pp. 186-191. , PID: 19595937spa
dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subjectAge Of Onsetspa
dc.subjectAlzheimer’S Diseasespa
dc.subjectExtreme Phenotypesspa
dc.subjectGenetic Isolatespa
dc.subject.ddcEnfermedadesspa
dc.subject.lembEnfermedad de Alzheimerspa
dc.subject.lembFenotiposspa
dc.subject.lembGenotiposspa
dc.titleTargeting neuroplasticity, cardiovascular, and cognitive-associated : Genomic variants in familial alzheimer’s diseasespa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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