期刊
ALZHEIMERS & DEMENTIA
卷 16, 期 9, 页码 1213-1223出版社
WILEY
DOI: 10.1002/alz.12092
关键词
Alzheimer's disease; amyloid beta; ADNI; CREB5; imaging genetics; microarray gene expression
资金
- NIH [U01AG024904, R01LM012535, R03AG054936, R01 AG19771, P30AG10133, R01LM011360, P50GM115318, NCATSUL1TR001108, K01 AG049050, RFAG051504, U01AG046139, U01 AG006786, U24AG021886, R03AG050856, U01AG057195]
- DOD [W81XWH-12-2-0012, W81XWH-14-2-0151]
- Alzheimer's Association
- Biomarkers Across Neurodegenerative Diseases
- Indiana Clinical and Translational Science Institute
- IU Health-IU School of Medicine Strategic Neuroscience Research Initiative
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, TMBIA46, IRAK3, and RPAIN) as significantly dysregulated in LOAD. The most significantly altered gene, CREB5, was also associated with brain atrophy and increased amyloid beta (A beta) accumulation, especially in the entorhinal cortex region. cis-expression quantitative trait loci mapping analysis of CREB5 detected five significant associations (P < 5 x 10(-8)), where rs56388170 (most significant) was also significantly associated with global cortical A beta deposition measured by [F-18]Florbetapir positron emission tomography and CSF A beta(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.
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