Genome-wide transcriptome analysis identifies novel dysregulated genes implicated in Alzheimer's pathology

Kwangsik Nho; Kelly Nudelman; Mariet Allen; Angela Hodges; Sungeun Kim; Shannon L. Risacher; Liana G. Apostolova; Kuang Lin; Katie Lunnon; Xue Wang; Jeremy D. Burgess; Nilüfer Ertekin-Taner; Ronald C. Petersen; Lisu Wang; Zhenhao Qi; Aiqing He; Isaac Neuhaus; Vishal Patel; Tatiana Foroud; Kelley M. Faber; Simon Lovestone; Andrew Simmons; Michael W. Weiner; Andrew J. Saykin

doi:10.1002/alz.12092

Genome-wide transcriptome analysis identifies novel dysregulated genes implicated in Alzheimer's pathology

Kwangsik Nho, Kelly Nudelman, Mariet Allen, Angela Hodges, Sungeun Kim, Shannon L. Risacher, Liana G. Apostolova, Kuang Lin, Katie Lunnon, Xue Wang, Jeremy D. Burgess, Nilüfer Ertekin-Taner, Ronald C. Petersen, Lisu Wang, Zhenhao Qi, Aiqing He, Isaac Neuhaus, Vishal Patel, Tatiana Foroud, Kelley M. FaberSimon Lovestone, Andrew Simmons, Michael W. Weiner, Andrew J. Saykin^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

Introduction: Abnormal gene expression patterns may contribute to the onset and progression of late-onset Alzheimer's disease (LOAD). Methods: We performed transcriptome-wide meta-analysis (N = 1440) of blood-based microarray gene expression profiles as well as neuroimaging and cerebrospinal fluid (CSF) endophenotype analysis. Results: We identified and replicated five genes (CREB5, CD46, TMBIM6, IRAK3, and RPAIN) as significantly dysregulated in LOAD. The most significantly altered gene, CREB5, was also associated with brain atrophy and increased amyloid beta (Aβ) accumulation, especially in the entorhinal cortex region. cis-expression quantitative trait loci mapping analysis of CREB5 detected five significant associations (P ' 5 × 10 ⁻⁸), where rs56388170 (most significant) was also significantly associated with global cortical Aβ deposition measured by [ ¹⁸F]Florbetapir positron emission tomography and CSF Aβ _1-42. Discussion: RNA from peripheral blood indicated a differential gene expression pattern in LOAD. Genes identified have been implicated in biological processes relevant to Alzheimer's disease. CREB, in particular, plays a key role in nervous system development, cell survival, plasticity, and learning and memory.

Original language	English
Pages (from-to)	1213-1223
Number of pages	11
Journal	Alzheimer's and Dementia
Volume	16
Issue number	9
DOIs	https://doi.org/10.1002/alz.12092
Publication status	Published - 1 Sept 2020

Keywords

ADNI
Alzheimer's disease
amyloid β
CREB5
imaging genetics
microarray gene expression

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/alz.12092

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Nho, K., Nudelman, K., Allen, M., Hodges, A., Kim, S., Risacher, S. L., Apostolova, L. G., Lin, K., Lunnon, K., Wang, X., Burgess, J. D., Ertekin-Taner, N., Petersen, R. C., Wang, L., Qi, Z., He, A., Neuhaus, I., Patel, V., Foroud, T., ... Saykin, A. J. (2020). Genome-wide transcriptome analysis identifies novel dysregulated genes implicated in Alzheimer's pathology. Alzheimer's and Dementia, 16(9), 1213-1223. https://doi.org/10.1002/alz.12092

@article{1a18cbd5579643999549a67673353298,

title = "Genome-wide transcriptome analysis identifies novel dysregulated genes implicated in Alzheimer's pathology",

abstract = "Introduction: Abnormal gene expression patterns may contribute to the onset and progression of late-onset Alzheimer's disease (LOAD). Methods: We performed transcriptome-wide meta-analysis (N = 1440) of blood-based microarray gene expression profiles as well as neuroimaging and cerebrospinal fluid (CSF) endophenotype analysis. Results: We identified and replicated five genes (CREB5, CD46, TMBIM6, IRAK3, and RPAIN) as significantly dysregulated in LOAD. The most significantly altered gene, CREB5, was also associated with brain atrophy and increased amyloid beta (Aβ) accumulation, especially in the entorhinal cortex region. cis-expression quantitative trait loci mapping analysis of CREB5 detected five significant associations (P ' 5 × 10 −8), where rs56388170 (most significant) was also significantly associated with global cortical Aβ deposition measured by [ 18F]Florbetapir positron emission tomography and CSF Aβ 1-42. Discussion: RNA from peripheral blood indicated a differential gene expression pattern in LOAD. Genes identified have been implicated in biological processes relevant to Alzheimer's disease. CREB, in particular, plays a key role in nervous system development, cell survival, plasticity, and learning and memory. ",

keywords = "ADNI, Alzheimer's disease, amyloid β, CREB5, imaging genetics, microarray gene expression",

author = "Kwangsik Nho and Kelly Nudelman and Mariet Allen and Angela Hodges and Sungeun Kim and Risacher, {Shannon L.} and Apostolova, {Liana G.} and Kuang Lin and Katie Lunnon and Xue Wang and Burgess, {Jeremy D.} and Nil{\"u}fer Ertekin-Taner and Petersen, {Ronald C.} and Lisu Wang and Zhenhao Qi and Aiqing He and Isaac Neuhaus and Vishal Patel and Tatiana Foroud and Faber, {Kelley M.} and Simon Lovestone and Andrew Simmons and Weiner, {Michael W.} and Saykin, {Andrew J.}",

year = "2020",

month = sep,

day = "1",

doi = "10.1002/alz.12092",

language = "English",

volume = "16",

pages = "1213--1223",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

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Nho, K, Nudelman, K, Allen, M, Hodges, A, Kim, S, Risacher, SL, Apostolova, LG, Lin, K , Lunnon, K, Wang, X, Burgess, JD, Ertekin-Taner, N, Petersen, RC, Wang, L, Qi, Z, He, A, Neuhaus, I, Patel, V, Foroud, T, Faber, KM, Lovestone, S , Simmons, A, Weiner, MW & Saykin, AJ 2020, 'Genome-wide transcriptome analysis identifies novel dysregulated genes implicated in Alzheimer's pathology', Alzheimer's and Dementia, vol. 16, no. 9, pp. 1213-1223. https://doi.org/10.1002/alz.12092

TY - JOUR

T1 - Genome-wide transcriptome analysis identifies novel dysregulated genes implicated in Alzheimer's pathology

AU - Nho, Kwangsik

AU - Nudelman, Kelly

AU - Allen, Mariet

AU - Hodges, Angela

AU - Kim, Sungeun

AU - Risacher, Shannon L.

AU - Apostolova, Liana G.

AU - Lin, Kuang

AU - Lunnon, Katie

AU - Wang, Xue

AU - Burgess, Jeremy D.

AU - Ertekin-Taner, Nilüfer

AU - Petersen, Ronald C.

AU - Wang, Lisu

AU - Qi, Zhenhao

AU - He, Aiqing

AU - Neuhaus, Isaac

AU - Patel, Vishal

AU - Foroud, Tatiana

AU - Faber, Kelley M.

AU - Lovestone, Simon

AU - Simmons, Andrew

AU - Weiner, Michael W.

AU - Saykin, Andrew J.

PY - 2020/9/1

Y1 - 2020/9/1

N2 - Introduction: Abnormal gene expression patterns may contribute to the onset and progression of late-onset Alzheimer's disease (LOAD). Methods: We performed transcriptome-wide meta-analysis (N = 1440) of blood-based microarray gene expression profiles as well as neuroimaging and cerebrospinal fluid (CSF) endophenotype analysis. Results: We identified and replicated five genes (CREB5, CD46, TMBIM6, IRAK3, and RPAIN) as significantly dysregulated in LOAD. The most significantly altered gene, CREB5, was also associated with brain atrophy and increased amyloid beta (Aβ) accumulation, especially in the entorhinal cortex region. cis-expression quantitative trait loci mapping analysis of CREB5 detected five significant associations (P ' 5 × 10 −8), where rs56388170 (most significant) was also significantly associated with global cortical Aβ deposition measured by [ 18F]Florbetapir positron emission tomography and CSF Aβ 1-42. Discussion: RNA from peripheral blood indicated a differential gene expression pattern in LOAD. Genes identified have been implicated in biological processes relevant to Alzheimer's disease. CREB, in particular, plays a key role in nervous system development, cell survival, plasticity, and learning and memory.

AB - Introduction: Abnormal gene expression patterns may contribute to the onset and progression of late-onset Alzheimer's disease (LOAD). Methods: We performed transcriptome-wide meta-analysis (N = 1440) of blood-based microarray gene expression profiles as well as neuroimaging and cerebrospinal fluid (CSF) endophenotype analysis. Results: We identified and replicated five genes (CREB5, CD46, TMBIM6, IRAK3, and RPAIN) as significantly dysregulated in LOAD. The most significantly altered gene, CREB5, was also associated with brain atrophy and increased amyloid beta (Aβ) accumulation, especially in the entorhinal cortex region. cis-expression quantitative trait loci mapping analysis of CREB5 detected five significant associations (P ' 5 × 10 −8), where rs56388170 (most significant) was also significantly associated with global cortical Aβ deposition measured by [ 18F]Florbetapir positron emission tomography and CSF Aβ 1-42. Discussion: RNA from peripheral blood indicated a differential gene expression pattern in LOAD. Genes identified have been implicated in biological processes relevant to Alzheimer's disease. CREB, in particular, plays a key role in nervous system development, cell survival, plasticity, and learning and memory.

KW - ADNI

KW - Alzheimer's disease

KW - amyloid β

KW - CREB5

KW - imaging genetics

KW - microarray gene expression

UR - http://www.scopus.com/inward/record.url?scp=85088940808&partnerID=8YFLogxK

U2 - 10.1002/alz.12092

DO - 10.1002/alz.12092

M3 - Article

AN - SCOPUS:85088940808

SN - 1552-5260

VL - 16

SP - 1213

EP - 1223

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 9

ER -

Genome-wide transcriptome analysis identifies novel dysregulated genes implicated in Alzheimer's pathology

Abstract

Keywords

UN SDGs

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