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Diffusion along Perivascular Spaces as a Marker for Glymphatic System Impairment in Huntington's Disease
Jin-Hui Yin1,2, Ling-Xiao Cao1,2, Ya-Ou Liu1,3
1Human Brain and Tissue Bank, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Insights
Glymphatic system function is impaired in Huntington's disease (HD) patients, with reduced diffusion along perivascular spaces (ALPS) correlating with disease severity and cognitive decline.
Area of Science:
- Neuroscience
- Neurodegenerative Diseases
- Biomarkers
Background:
- Huntington's disease (HD) is a progressive neurodegenerative disorder.
- Glymphatic system dysfunction is implicated in various neurological conditions.
- Investigating glymphatic function in HD is crucial for understanding disease mechanisms.
Purpose of the Study:
- To determine if glymphatic function is impaired in individuals with Huntington's disease.
- To assess the clinical relevance of glymphatic dysfunction in HD.
Main Methods:
- Recruited 49 subjects with mutant Huntingtin (mHTT) (35 manifest HD, 14 pre-manifest HD) and 35 healthy controls (HC).
- Measured diffusion along perivascular spaces (ALPS) index and percentage of perivascular space in basal ganglia (pPVS_BG).
- Utilized receiver operating characteristic (ROC) analysis and correlation analyses to evaluate ALPS index's diagnostic and clinical relevance.
Main Results:
- ALPS index was significantly decreased in mHTT carriers compared to HCs, and further reduced in manifest HD versus pre-manifest HD.
- ALPS index effectively discriminated between mHTT carriers and HCs, manifest and pre-manifest HD, and pre-manifest HD and controls.
- Lower ALPS index correlated with increased disease burden, severity, larger pPVS_BG, reduced brain volume, and thinner cortices.
- ALPS index predicted motor and cognitive function performance and partially mediated the effects of CAG repeat and age on cognitive decline.
Conclusions:
- Glymphatic system impairment is evident in Huntington's disease patients.
- This impairment, particularly in paraventricular white matter and basal ganglia, correlates with clinical symptoms, disease burden, and brain structural changes.
- ALPS index serves as a potential biomarker for glymphatic dysfunction in HD.
Background:
The aim was to investigate if glymphatic function is impaired in patients with Huntington's disease (HD) and its clinical relevance.
Methods:
Forty-nine subjects carrying mutant Huntingtin (mHTT), comprising 35 manifest (mHD) and 14 pre-manifest (PreHD), and 35 healthy controls (HC) were recruited in this study. The diffusion along perivascular spaces (ALPS) index and the percentage of perivascular space in the basal ganglia (pPVS_BG) were obtained in different groups. The discrimination effects of ALPS index were detected using receiver operating characteristic (ROC) analysis, and the correlations of ALPS index with clinical features of HD were further analyzed.
Results:
ALPS index was decreased in mHTT carriers compared to HCs, and it was lower in mHD compared to PreHD patients. ROC analysis showed that the ALPS index could discriminate mHTT from HC (AUC [area under the curve] = 0.903), mHD from PreHD (AUC = 0.886), and PreHD from controls (AUC = 0.755). Lower ALPS index correlated with greater disease burden, severity of the disease, lager pPVS_BG, and lower brain volume and thickness of cortices. Regression analysis showed that ALPS index could predict the performance of motor and cognitive functions. Mediation analysis revealed that ALPS partially mediated the effects of CAG repeat and age on the cognitive decline in HD.
Conclusions:
This study demonstrated that the impairment of the glymphatic system, especially in the paraventricular white matter and BG, was correlated with the clinical manifestations, disease burden, and brain structural changes in mHTT carriers. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
