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

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

The 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 iso...

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Autores Principales:	Vélez, Jorge I., Lopera, Francisco, Creagh, Penelope K., Piñeros, Laura B., Das, Debjani, Cervantes-Henríquez, Martha L., Acosta-López, Johan E., Isaza-Ruget, Mario A., Espinosa, Lady G., Easteal, Simon, Quintero-Hernandez, Gustavo-Adolfo, Tamar Silva, Claudia, Mastronardi, Claudio, Arcos-Burgos, Mauricio
Formato:	Artículo (Article)
Lenguaje:	Inglés (English)
Publicado:	2018
Materias:	Age Of Onset Alzheimer’S Disease Extreme Phenotypes Genetic Isolate Enfermedades Enfermedad de Alzheimer Fenotipos Genotipos
Acceso en línea:	http://repository.urosario.edu.co/handle/10336/19120

id	ir-10336-19120
recordtype	dspace
spelling	ir-10336-191202019-09-19T12:37:54Z Targeting neuroplasticity, cardiovascular, and cognitive-associated : Genomic variants in familial alzheimer’s disease Vélez, Jorge I. Lopera, Francisco Creagh, Penelope K. Piñeros, Laura B. Das, Debjani Cervantes-Henríquez, Martha L. Acosta-López, Johan E. Isaza-Ruget, Mario A. Espinosa, Lady G. Easteal, Simon Quintero-Hernandez, Gustavo-Adolfo Tamar Silva, Claudia Mastronardi, Claudio Arcos-Burgos, Mauricio Age Of Onset Alzheimer’S Disease Extreme Phenotypes Genetic Isolate Enfermedades Enfermedad de Alzheimer Fenotipos Genotipos The 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 APOEE2 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 APOEE2 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). 2018 2019-02-20T20:14:29Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 0893-7648 http://repository.urosario.edu.co/handle/10336/19120 10.1007/s12035-018-1298-z eng info:eu-repo/semantics/openAccess application/pdf Brookmeyer, 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: 19595937
institution	EdocUR - Universidad del Rosario
collection	DSpace
language	Inglés (English)
topic	Age Of Onset Alzheimer’S Disease Extreme Phenotypes Genetic Isolate Enfermedades Enfermedad de Alzheimer Fenotipos Genotipos
spellingShingle	Age Of Onset Alzheimer’S Disease Extreme Phenotypes Genetic Isolate Enfermedades Enfermedad de Alzheimer Fenotipos Genotipos Vélez, Jorge I. Lopera, Francisco Creagh, Penelope K. Piñeros, Laura B. Das, Debjani Cervantes-Henríquez, Martha L. Acosta-López, Johan E. Isaza-Ruget, Mario A. Espinosa, Lady G. Easteal, Simon Quintero-Hernandez, Gustavo-Adolfo Tamar Silva, Claudia Mastronardi, Claudio Arcos-Burgos, Mauricio Targeting neuroplasticity, cardiovascular, and cognitive-associated : Genomic variants in familial alzheimer’s disease
description	The 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 APOEE2 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 APOEE2 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).
format	Artículo (Article)
author	Vélez, Jorge I. Lopera, Francisco Creagh, Penelope K. Piñeros, Laura B. Das, Debjani Cervantes-Henríquez, Martha L. Acosta-López, Johan E. Isaza-Ruget, Mario A. Espinosa, Lady G. Easteal, Simon Quintero-Hernandez, Gustavo-Adolfo Tamar Silva, Claudia Mastronardi, Claudio Arcos-Burgos, Mauricio
author_facet	Vélez, Jorge I. Lopera, Francisco Creagh, Penelope K. Piñeros, Laura B. Das, Debjani Cervantes-Henríquez, Martha L. Acosta-López, Johan E. Isaza-Ruget, Mario A. Espinosa, Lady G. Easteal, Simon Quintero-Hernandez, Gustavo-Adolfo Tamar Silva, Claudia Mastronardi, Claudio Arcos-Burgos, Mauricio
author_sort	Vélez, Jorge I.
title	Targeting neuroplasticity, cardiovascular, and cognitive-associated : Genomic variants in familial alzheimer’s disease
title_short	Targeting neuroplasticity, cardiovascular, and cognitive-associated : Genomic variants in familial alzheimer’s disease
title_full	Targeting neuroplasticity, cardiovascular, and cognitive-associated : Genomic variants in familial alzheimer’s disease
title_fullStr	Targeting neuroplasticity, cardiovascular, and cognitive-associated : Genomic variants in familial alzheimer’s disease
title_full_unstemmed	Targeting neuroplasticity, cardiovascular, and cognitive-associated : Genomic variants in familial alzheimer’s disease
title_sort	targeting neuroplasticity, cardiovascular, and cognitive-associated : genomic variants in familial alzheimer’s disease
publishDate	2018
url	http://repository.urosario.edu.co/handle/10336/19120
_version_	1645142125276299264
score	12,352018

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

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