Brain aging in Type II GM1 gangliosidosis

Area of Science:

• Neuroimaging
• Neurodegenerative Diseases
• Lysosomal Storage Disorders

Background:

• GM1 gangliosidosis is a fatal inherited neurodegenerative lysosomal storage disorder with no current treatments.
• Assessing neuronal degeneration is critical for understanding disease progression in GM1 gangliosidosis.

Purpose of the Study:

• To evaluate the utility of MRI-based predicted brain age for assessing neurodegeneration in GM1 gangliosidosis.
• To explore predicted brain age and Brain Structures Age Gap Estimation (BSAGE) as potential neuroimaging outcome measures for clinical trials.

Main Methods:

• Utilized a machine learning pipeline (BrainStructuresAges) to calculate predicted brain age and BSAGE.
• Analyzed 81 MRI scans from 41 Type II GM1 gangliosidosis patients (juvenile and late-infantile) and 897 scans from 556 neurotypical controls.
• Correlated predicted brain age and BSAGE with clinical outcome assessments.

Main Results:

• GM1 gangliosidosis patients exhibited significantly accelerated brain aging compared to neurotypical controls.
• Accelerated aging was observed in key brain structures including the thalamus, caudate nucleus, cerebellum, and brainstem.
• BSAGE values were substantially higher in late-infantile (35.50 years) and juvenile (21.19 years) GM1 cohorts compared to controls (0.03 years).

Conclusions:

• MRI-based predicted brain age accurately reflects the neurodegenerative progression in Type II GM1 disease subtypes.
• Predicted brain aging metrics correlate with clinical outcomes, suggesting their potential as neuroimaging outcome measures.
• This approach may be valuable for evaluating treatment efficacy in clinical trials for GM1 gangliosidosis.