Journal
MOLECULAR NEUROBIOLOGY
Volume 53, Issue 8, Pages 5772-5781Publisher
HUMANA PRESS INC
DOI: 10.1007/s12035-015-9484-8
Keywords
Alzheimer's disease; MicroRNA; Expression profiles; beta-site APP cleaving enzyme
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Funding
- National Basic Research Development Program of China [2010CB945200, 2011CB504104]
- National Natural Science Foundation of China [81371218, 81001426, 81070958, 81171027, 81200842, 81573401, 91332107]
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A series of investigations have been performed regarding microRNA (miRNA, miR) of Alzheimer's disease (AD) patients. However, most of these used microarray with neither validation by PCR nor any follow-up on the biological mechanism implicated by findings. Further, there were rarely any analyses linking clinical phenotype of de novo, drug-naive patients to cellular pathogenic mechanism(s) to date. Microarray screening followed by validation via quantitative PCR (Q-PCR) assays and the relationship between miRNAs and phenotypic indices were evaluated. Additionally, the cellular mechanism of miRNAs through effects of beta-site amyloid precursor protein (APP) cleaving enzyme (BACE1) was assessed. We identified 2 specific differentially expressed (DE) miRNAs (miR-339 and miR-425) as potential diagnostic biomarkers for AD and revealed that these DE miRNAs could be involved in modulating the pathogenesis of AD via BACE1 protein inhibition. The findings presented here reveal a detailed snapshot of the profile of peripheral blood mononuclear cells (PBMC) miRNA changes in AD patients, association with clinical phenotype, and potential roles in cellular pathogenesis.
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