Abstract #2978

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

Alexia Solomon^1,2, Zexi Wang^1,3, and Jingwen Yao^1,3,4

¹UCLA Brain Tumor Imaging Laboratory (BTIL), University of California, Los Angeles, Los Angeles, CA, United States, ²Charlie Dunlop School of Biological Sciences, University of California, Irvine, Irvine, CA, United States, ³Department of Radiological Sciences, University of California, Los Angeles, Los Angeles, CA, United States, ⁴Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, Los Angeles, CA, United States

Synopsis

Keywords: Other Neurodegeneration, Neurodegeneration, Huntington's Disease; DTI-ALPS; Biomarkers

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.

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