Aintzane Urbizu, Spain
Research Institute Germans Trias i Pujol PathologyAuthor Of 1 Presentation
DOES ABNORMAL PLATELET ACTIVATION CONTRIBUTE TO THE DEVELOPMENT OF DEMENTIA WITH LEWY BODIES?
Abstract
Aims
To identify the possible effect of downregulated platelet-derived miRNAs in dementia with Lewy bodies (DLB) on brain function-related mRNAs expressed in platelets and to compare expression pattern with Alzheimer disease (AD).
Methods
Total RNA was purified from platelets obtained from DLB, AD and control cases. Eight samples of each group were analyzed with nCounter Neuropathology panel including 770 mRNAs, by subjecting 75 ng of total RNA to profiling by NanoString-technology. Expression changes of 49 mRNAs were validated in 20 independent DLB, AD and control samples by a custom nCounter panel. Results were evaluated by nSolver software (NanoString), deltadeltaCt method, String and Reactome Databases.
Results
Of the 770 mRNAs included in the panel, 457 were expressed in DLB. Ninety-six mRNAs were overexpressed and related to neuronal plasticity and platelet activation. Of 78 down-regulated genes, 31 were related the immune system and 9 to transcription factor binding. Validation of the 26 most up-regulated and 23 most down-regulated genes revealed overexpression of APP, ACTN1, CD9, DGKE, EGF and P2RY12 (platelet activation), and RTN4, APP, NPTN, CA2, SLC6A4, SLC18A2, HSPB1 (neuronal plasticity). CCR5, IL13RA1, HSPA6, NFKBIB, ITGAX and TNFRSF1B (immune system) and JUN, PCNA, TAF4 and SPI1 (transcription factor binding) were down-regulated in DLB. Platelet-activation-related genes overexpressed in DLB were down-regulated in AD indicating that abnormal platelet activation may be a key event in DLB pathogenesis.
Conclusions
The expression of platelet-derived mRNAs is altered in DLB and differs from AD. Involvement of platelet activation in DLB pathogenesis should be further explored.