P1‐212: Alzheimer's Disease Hippocampus Micro‐RNA Expression

Résumé fourni par la source

MicroRNAs play an essential role in gene regulation in the brain. However, little is known about their role in neurodegenerative diseases, such as late-onset Alzheimer's disease (AD). Characterizing expression profiles of microRNA in AD brain may help elucidate the role of microRNA in the pathophysiology of AD and may lead to identification of AD specific biomarkers. The aim of this exploratory investigation was to determine if AD hippocampus microRNAs are differentially expressed compared to AD cerebellum, control hippocampus or control cerebellum. First, post-mortem brain samples were pooled to measure multiple microRNA (n = 377) levels using microRNA arrays. Pooled samples consisted of AD hippocampus, AD cerebellum, control hippocampus, or control cerebellum (n = 21 each). Second, individual post-mortem brain AD and control samples, consisting of a subset of the pooled sample, were used in qRT-PCR assays to further explore differences in microRNA levels between subjects and according to APOE e4 genotype, gender, amyloid plaque score or Braak stage. In addition, in silico analyses were performed to predict target genes for differentially expressed microRNAs. We found several microRNA (n = 20) to be differentially expressed in the AD hippocampus compared to controls using microRNA arrays. Many of these 20 microRNA are predicted to target AD relevant genes (i.e. ADAM10, APP, BACE1, MAPT, PSEN1 and PSEN2). A subset of these 20 microRNA were measured using qRT-PCR, of which three microRNA; miR-15a, miR-330-3p, miR-501-5p, are strongly associated with hippocampus expression compared to cerebellum, independent of disease status. MiR-15a level is associated with APOE e4. MiR-330-3p level is associated with gender, amyloid plaque score and Braak stage. MiR-501-5p level is associated with APOE e4, gender and amyloid plaque score. In conclusion, this investigation demonstrates that microRNA levels are differentially expressed according to brain region and are associated with APOE e4, amyloid plaque score and Braak stage. MicroRNA identified in this exploratory study are predicted to target AD relevant genes and thus may warrant further investigation into their functional impact on expression and their utility as biomarkers of neurodegenerative disease.

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