한빛사논문
- 조회1,726
Kwangsik Nho, Ph.D.1,2,3, Kelly Nudelman, Ph.D.1,3,11,12, Mariet Allen, Ph.D.6, Angela Hodges, Ph.D.4, Sungeun Kim, Ph.D.1,2,3, Shannon L. Risacher, Ph.D.1,3, Liana Apostolova, M.D.1,3, Kuang Lin, Ph.D.4, Katie Lunnon, Ph.D.5 Xue Wang, Ph.D.7, Jeremy D. Burgess6, Nilüfer Ertekin-Taner, M.D., Ph.D.6,8, Ronald C. Petersen, M.D., Ph.D.9, Lisu Wang, M.D.10, Zhenhao Qi, Ph.D.10, Aiqing He, M.D.10, Isaac Neuhaus10, Vishal Patel10, Tatiana Foroud, Ph.D.1,2,3,11,12, Kelley M. Faber12, Simon Lovestone, Ph.D.13, Andrew Simmons, Ph.D.13, Michael W. Weiner, M.D.14,15, and Andrew J. Saykin, Psy.D.1,3,11*
1Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA;
2Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA;
3Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA
4Institute of Psychiatry, Psychology & Neuroscience, King’s college London, London, UK;
5University of Exeter Medical School, Exeter, UK;
6Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA;
7Department of Health Sciences Research, Mayo Clinic Florida, Jacksonville, FL, USA;
8Department of Neurology, Mayo Clinic Florida, Jacksonville, FL, USA;
9Department of Neurology, Mayo Clinic Minnesota, Rochester, MN, USA;
10Bristol-Meyers Squibb, Wallingford, CT, USA
11Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA;
12National Cell Repository for Alzheimer’s Disease, IN, USA;
13Institute of Psychiatry, King’s College London, London, UK;
14Departments of Radiology, Medicine, and Psychiatry, University of California-San Francisco, San Francisco, CA, USA;
15Department of Veterans Affairs Medical Center, San Francisco, CA, USA
*Corresponding author
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 Aβ1‐42.
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.
논문정보
- Research article
- 2020년 08월 (BRIC 등록일 2020-08-19)
- 국외 연구진
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