D007 Translatable plasma and CSF biomarkers for use in mouse models of Huntington’s disease

<h3>Background</h3> Monitoring plasma and CSF biomarkers of neuronal impairment in HD mice enhances our understanding of disease progression and facilitates potential therapeutic strategies for HD. <h3>Aims</h3> To better understand how plasma and CSF biomarker levels change with disease progression in HD mice. <h3>Methods</h3> Plasma was collected from R6/2:Q200 and WT at 4, 8 and 12 weeks, from R6/2:Q90 and WT at 4, 14 and 24 weeks and zQ175, YAC128 and respective WT mice at 2, 6 and 12 month. CSF was collected from the cisterna magna from R6/2:Q200 and WT at 12 weeks of age, from R6/2:Q90 and WT at 16 and 24 weeks of age, from zQ175, YAC128 and respective WT mice at 6 and 12 months. NEFL, Total-Tau and BRP-39 concentrations were quantified using the HD-1 (SIMOA, Quanterix). <h3>Results</h3> Quanterix analysis revealed elevated levels of plasma NEFL and BRP-39: in R6/2:Q200 at 8 and 12 weeks of age, in R6/2:Q90 at 4 (NEFL only), 14 and 24 weeks of age, in zQ175 at 6 and 12 months of age and in YAC128 at 6 (BRP-39 only) and 12 months of age compared to WT littermates. CSF NEFL levels were elevated in R6/2:Q200 at 12 weeks of age, in R6/2:Q90 at 16 and 24 weeks of age, in zQ175 at 6 and 12 months of age and in YAC128 at 6 (BRP-39 only) and 12 months of age compared to WT littermates. Plasma and CSF Tau levels were only elevated in HD mice as compared to WT littermates at late disease stage.