Work

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

Year: 2024

Type: conference-paper

Abstract: Background Monitoring plasma and CSF biomarkers of neuronal impairment in HD mice enhances our understanding of disease progression and facilitates potential therapeutic strategies for HD. Aims To better understand how plasma and CSF biomarker levels change with disease progression in HD mice. Methods 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). Results 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.

DOI: 10.1136/jnnp-2024-ehdn.82