Genome‐wide transcriptome analysis identifies novel dysregulated genes implicated in Alzheimer's pathology
Year: 2020
Type: article
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.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.12092
Authors: 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, for the Alzheimer's Disease Neuroimaging Initiative
Institutions: Indiana University Indianapolis, Indiana University School of Medicine, Indiana University, Mayo Clinic in Florida, King's College London, State University of New York at Oswego, University of Exeter, Mayo Clinic, Bristol-Myers Squibb (United States), University of Oxford, San Francisco VA Medical Center, United States Department of Veterans Affairs, University of California, San Francisco, Alzheimer’s Disease Neuroimaging Initiative
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G104586243, G107491585, G1221608705, G1309605592, Indiana Alzheimer Disease Center, G1576357080, Integrative translational discovery of vascular risk factors in aging and dementia, G2212362641, G2908616768, G2957681590, Sensory and Perceptual Measures as Biomarkers of Alzheimer's Disease Pathology, G3072607366, Pharmacogenomics of Statin Therapy, THE NCAA-DOD GRAND ALLIANCE: CONCUSSION ASSESSMENT, RESEARCH, AND EDUCATION (CARE) CONSORTIUM, G5056103449, EFFECTS OF TRAUMATIC BRAIN INJURY (TBI) AND POST TRAUMATIC STRESS DISORDER (PTSD) ON ALZHEIMER'S DISEASE (AD) IN VETERANS USING IMAGING AND BIOMARKERS IN THE AD NEUROIMAGING INITIATIVE (ADNI)", Novel Strategies for Blood-based Biomarkers for AD: Role of Genetic Variation in a Multivariate Framework, G801680829, G849165527, G9000006734, G9000014109, G9000033611, G9000039018, G9000059087, G9000064957, G9000071044, G9000077669, G9000122267, G9000128249, G9000130884, Ultrascale Machine Learning to Empower Discovery in Alzheimers Disease Biobanks
OpenAlex ID: W3013706956