Glymphatic Dysfunction in Huntington’s Disease: DTI-ALPS as a Biomarker for Progression and Symptom Severity

Motivation: Huntington's disease causes neurodegeneration linked to toxic protein buildup. Identifying glymphatic dysfunction as a biomarker could improve detection, informing interventions targeting the glymphatic system. Goal(s): This study investigates whether glymphatic dysfunction, indicated by lower diffusion tensor image analysis along the perivascular space (DTI-ALPS), is present in HD patients and correlates with symptoms. Approach: Using DTI-ALPS, a non-invasive imaging technique, we assessed glymphatic function in 287 subjects, comparing healthy, pre-manifest, and manifest HD groups, and correlating scores with motor and cognitive performance. Results: HD patients exhibit lower DTI-ALPS scores, manifest HD showing the most decline. Lower ALPS correlated with greater motor and cognitive impairments. Impact: This research positions DTI-ALPS reduction as a promising biomarker for glymphatic dysfunction in HD, correlating with disease severity and symptoms. DTI-ALPS could enhance understanding of HD pathogenesis, support clinical monitoring of glymphatic dysfunction, and potentially inform targeted interventions.