Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-β deposition in Alzheimer’s disease

Abstract Background The interaction between the brain and periphery might play a crucial role in the development of Alzheimer’s disease (AD). Methods Using blood transcriptomic profile data from two independent AD cohorts, we performed expression quantitative trait locus (cis-eQTL) analysis of 29 si...

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Autores principales:	Young Ho Park, Jung-Min Pyun, Angela Hodges, Jae-Won Jang, Paula J. Bice, SangYun Kim, Andrew J. Saykin, Kwangsik Nho, for the AddNeuroMed consortium and the Alzheimer’s Disease Neuroimaging Initiative
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Alzheimer’s disease Transcriptome Blood Expression quantitative trait locus Genome-wide association study Expression Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/336e0a70dfa542ebbdfc9af946dc5ecc
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spelling	oai:doaj.org-article:336e0a70dfa542ebbdfc9af946dc5ecc2021-11-08T11:15:39ZDysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-β deposition in Alzheimer’s disease10.1186/s13195-021-00919-z1758-9193https://doaj.org/article/336e0a70dfa542ebbdfc9af946dc5ecc2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13195-021-00919-zhttps://doaj.org/toc/1758-9193Abstract Background The interaction between the brain and periphery might play a crucial role in the development of Alzheimer’s disease (AD). Methods Using blood transcriptomic profile data from two independent AD cohorts, we performed expression quantitative trait locus (cis-eQTL) analysis of 29 significant genetic loci from a recent large-scale genome-wide association study to investigate the effects of the AD genetic variants on gene expression levels and identify their potential target genes. We then performed differential gene expression analysis of identified AD target genes and linear regression analysis to evaluate the association of differentially expressed genes with neuroimaging biomarkers. Results A cis-eQTL analysis identified and replicated significant associations in seven genes (APH1B, BIN1, FCER1G, GATS, MS4A6A, RABEP1, TRIM4). APH1B expression levels in the blood increased in AD and were associated with entorhinal cortical thickness and global cortical amyloid-β deposition. Conclusion An integrative analysis of genetics, blood-based transcriptomic profiles, and imaging biomarkers suggests that APH1B expression levels in the blood might play a role in the pathogenesis of AD.Young Ho ParkJung-Min PyunAngela HodgesJae-Won JangPaula J. BiceSangYun KimAndrew J. SaykinKwangsik Nhofor the AddNeuroMed consortium and the Alzheimer’s Disease Neuroimaging InitiativeBMCarticleAlzheimer’s diseaseTranscriptomeBloodExpression quantitative trait locusGenome-wide association studyExpressionNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENAlzheimer’s Research & Therapy, Vol 13, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer’s disease Transcriptome Blood Expression quantitative trait locus Genome-wide association study Expression Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Alzheimer’s disease Transcriptome Blood Expression quantitative trait locus Genome-wide association study Expression Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Young Ho Park Jung-Min Pyun Angela Hodges Jae-Won Jang Paula J. Bice SangYun Kim Andrew J. Saykin Kwangsik Nho for the AddNeuroMed consortium and the Alzheimer’s Disease Neuroimaging Initiative Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-β deposition in Alzheimer’s disease
description	Abstract Background The interaction between the brain and periphery might play a crucial role in the development of Alzheimer’s disease (AD). Methods Using blood transcriptomic profile data from two independent AD cohorts, we performed expression quantitative trait locus (cis-eQTL) analysis of 29 significant genetic loci from a recent large-scale genome-wide association study to investigate the effects of the AD genetic variants on gene expression levels and identify their potential target genes. We then performed differential gene expression analysis of identified AD target genes and linear regression analysis to evaluate the association of differentially expressed genes with neuroimaging biomarkers. Results A cis-eQTL analysis identified and replicated significant associations in seven genes (APH1B, BIN1, FCER1G, GATS, MS4A6A, RABEP1, TRIM4). APH1B expression levels in the blood increased in AD and were associated with entorhinal cortical thickness and global cortical amyloid-β deposition. Conclusion An integrative analysis of genetics, blood-based transcriptomic profiles, and imaging biomarkers suggests that APH1B expression levels in the blood might play a role in the pathogenesis of AD.
format	article
author	Young Ho Park Jung-Min Pyun Angela Hodges Jae-Won Jang Paula J. Bice SangYun Kim Andrew J. Saykin Kwangsik Nho for the AddNeuroMed consortium and the Alzheimer’s Disease Neuroimaging Initiative
author_facet	Young Ho Park Jung-Min Pyun Angela Hodges Jae-Won Jang Paula J. Bice SangYun Kim Andrew J. Saykin Kwangsik Nho for the AddNeuroMed consortium and the Alzheimer’s Disease Neuroimaging Initiative
author_sort	Young Ho Park
title	Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-β deposition in Alzheimer’s disease
title_short	Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-β deposition in Alzheimer’s disease
title_full	Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-β deposition in Alzheimer’s disease
title_fullStr	Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-β deposition in Alzheimer’s disease
title_full_unstemmed	Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-β deposition in Alzheimer’s disease
title_sort	dysregulated expression levels of aph1b in peripheral blood are associated with brain atrophy and amyloid-β deposition in alzheimer’s disease
publisher	BMC
publishDate	2021
url	https://doaj.org/article/336e0a70dfa542ebbdfc9af946dc5ecc
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Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-β deposition in Alzheimer’s disease

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