In:
Alzheimer's & Dementia, Wiley, Vol. 16, No. 9 ( 2020-09), p. 1213-1223
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1552-5260
,
1552-5279
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2201940-6
