A46 Neurodegenerative markers in hd: association with clinical charactersitcs, triplet expansion, phenoconversion and mediterranean diet adherence

Abstract

Background Huntington’s disease (HD) is an inherited autosomal dominant neurodegenerative disorder. Common pathological molecular mechanisms contributing to HD include reactive oxygen species (ROS), mitochondrial dysfunction and neuro-inflammation.1 Exposure to the Mediterranean Diet (MD) provides neuroprotection and has anti-oxidant and anti-inflammatory properties.2–4 Adherence to the MD could positively influence age of onset and progression of HD. Aims to address gaps in understanding on how neurodegeneration mechanisms influence phenoconversion and clinical characteristics of HD, particularly age of onset to investigate how adherence to the Mediterranean diet may modify these associations to delay phenoconversion. Methods This is a case-control study, where HD cases, pre-symptomatic, early symptomatic and later stage and age-matched controls will be recruited. Questionnaires will be used to collect data. A blood sample will be collected for untargeted metabolomic investigation into the pathways involved in HD and pathways affected by the MD. An attempt was made to integrate existing publically available data on HD, to identify pathways which, play a role in disease pathology of HD. Enrichment analysis was performed and seven clusters with pathways involved in HD were obtained.5 Results/outcomes Some of the pathways identified through publicly available datasets were cAMP, TGF-beta, Ca2+, and VEGF. These are likely to play a role in contributing to disease pathogenesis of HD. Conclusions Given the existing results and those that will emerge from the untargeted metabolomic analysis, we hope to identify pathways that can differentiate between different HD disease stages and whose aberrant changes can be positively influenced by adherence to the MD. References . Mo C, Hannan A, Renoir T. Environmental factors as modulators of neurodegeneration: Insights from gene–environment interactions in Huntington’s disease. Neuroscience & Biobehavioral2015;52:178–192. . Sofi F, Macchi C, Casini A. Mediterranean diet and minimizing neurodegeneration. Curr Nutr Rep2013;2:75–80. . Valls-Pedret C, et al. Mediterranean diet and age-related cognitive decline. JAMA Internal Medicine2015;175(7):1094. . Casamenti F, Stefani M. Olive polyphenols: New promising agents to combat aging-associated neurodegeneration. Expert Review of Neurotherapeutics2016;17(4):345–358. . Andrea C, Kakouri, Christiana C, Christodoulou, et al. Revealing clusters of connected pathways through multisource data integration in Huntington’s disease and Spastic Ataxia (paper is currently under review) 2018.