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Genome‐wide transcriptome analysis identifies novel dysregulated genes implicated in Alzheimer's pathology
Author(s) -
Nho Kwangsik,
Nudelman Kelly,
Allen Mariet,
Hodges Angela,
Kim Sungeun,
Risacher Shan L.,
Apostolova Liana G.,
Lin Kuang,
Lun Katie,
Wang Xue,
Burgess Jeremy D.,
ErtekinTaner Nilüfer,
Petersen Ronald C.,
Wang Lisu,
Qi Zhenhao,
He Aiqing,
Neuhaus Isaac,
Patel Vishal,
Foroud Tatiana,
Faber Kelley M.,
Lovestone Simon,
Simmons Andrew,
Weiner Michael W.,
Saykin Andrew J.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12092
Subject(s) - transcriptome , biology , clusterin , gene expression , microarray analysis techniques , microarray , gene expression profiling , gene , entorhinal cortex , subependymal zone , neuroscience , pathology , genetics , hippocampus , medicine , apoptosis
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 [ 18 F]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.