RGS2 expression predicts amyloid-ß sensitivity, MCI and Alzheimer's disease: genome-wide transcriptomic profiling and bioinformatics data mining.
Transl Psychiatry
; 6(10): e909, 2016 10 04.
Article
em En
| MEDLINE
| ID: mdl-27701409
ABSTRACT
Alzheimer's disease (AD) is the most frequent cause of dementia. Misfolded protein pathological hallmarks of AD are brain deposits of amyloid-ß (Aß) plaques and phosphorylated tau neurofibrillary tangles. However, doubts about the role of Aß in AD pathology have been raised as Aß is a common component of extracellular brain deposits found, also by in vivo imaging, in non-demented aged individuals. It has been suggested that some individuals are more prone to Aß neurotoxicity and hence more likely to develop AD when aging brains start accumulating Aß plaques. Here, we applied genome-wide transcriptomic profiling of lymphoblastoid cells lines (LCLs) from healthy individuals and AD patients for identifying genes that predict sensitivity to Aß. Real-time PCR validation identified 3.78-fold lower expression of RGS2 (regulator of G-protein signaling 2; P=0.0085) in LCLs from healthy individuals exhibiting high vs low Aß sensitivity. Furthermore, RGS2 showed 3.3-fold lower expression (P=0.0008) in AD LCLs compared with controls. Notably, RGS2 expression in AD LCLs correlated with the patients' cognitive function. Lower RGS2 expression levels were also discovered in published expression data sets from postmortem AD brain tissues as well as in mild cognitive impairment and AD blood samples compared with controls. In conclusion, Aß sensitivity phenotyping followed by transcriptomic profiling and published patient data mining identified reduced peripheral and brain expression levels of RGS2, a key regulator of G-protein-coupled receptor signaling and neuronal plasticity. RGS2 is suggested as a novel AD biomarker (alongside other genes) toward early AD detection and future disease modifying therapeutics.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Expressão Gênica
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Peptídeos beta-Amiloides
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Emaranhados Neurofibrilares
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Placa Amiloide
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Proteínas RGS
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Perfilação da Expressão Gênica
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Estudo de Associação Genômica Ampla
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Mineração de Dados
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Doença de Alzheimer
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Limite:
Aged
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Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article