Genome-wide transcriptome analysis identifies novel dysregulated genes implicated in Alzheimer's pathology.
Alzheimers Dement
; 16(9): 1213-1223, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32755048
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 (Aß) 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 Aß deposition measured by [18 F]Florbetapir positron emission tomography and CSF Aß1-42 .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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Perfilação da Expressão Gênica
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Proteína A de Ligação a Elemento de Resposta do AMP Cíclico
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Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article