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Non-coding RNAs in neurodegeneration

Final Report Summary - NCRNANEURO (Non-coding RNAs in neurodegeneration)

The main goal:

The goal of the project 'Non-coding RNAs in neurodegeneration' was to find differentially expressed microRNAs in the brains of Alzheimer's Disease patients. We obtained 49 human brain samples from the Netherlands and 64 additional samples from England. The Dutch cohort corresponded to 7 prefrontal cortex samples belonging to each of the 6 Braak stages and to 7 additional controls. The English cohort was made of hippocampal samples from 23 controls and 42 late-onset Alzheimer's Disease patients.

The main result:

Profiling of miRNAs in the prefrontal cortex of the Dutch cohort using the nCounter multiplexing technology and time-course analysis showed expression changes of 33 miRNAs starting at early Braak stages, therefore showing that deregulation of miRNAs was not a passive consequence and late event during the disease. In the hippocampus, we found 38 miRNAs deregulated, allowing a classification of these sporadic cases at high accuracy and specificity. After intersection of the two datasets and validation by real-time PCR, we identified four miRNAs including miR-132, -129-5p, -136 and -92b as being consistently altered between controls and Alzheimer's Disease patients. Our result unequivocally demonstrated a down-regulation of miR-132 in neurons of Alzheimer's Disease patients showing Tau hyperphosphorylation and we further provided evidence that down-regulation of miR-132 may contribute to disease progression partially through aberrant expression of mRNA targets found in the Tau pathway.

Conclusions and socio-economic impacts of the project:

MicroRNAs are regarded as potential biomarkers of disease. We found 4 miRNAs that could represent specific markers of Alzheimer's Disease or of neurodegenerative disorders. This study adds an additional tool for the clinical detection of Alzheimer's Disease together with pre-established biomarkers of the disease such as amyloid beta and hyperphosphorylated Tau.