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 journalArticlepeer-review

25 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 languageEnglish
Pages (from-to)1213-1223
Number of pages11
JournalAlzheimer's and Dementia
Volume16
Issue number9
DOIs
Publication statusPublished - 1 Sept 2020

Keywords

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

Fingerprint

Dive into the research topics of 'Genome-wide transcriptome analysis identifies novel dysregulated genes implicated in Alzheimer's pathology'. Together they form a unique fingerprint.

Cite this