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Related Concept Videos

Parkinson Disease ll: Pathophysiology01:24

Parkinson Disease ll: Pathophysiology

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Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
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Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show...
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TRANSIENT ALTERATIONS IN THALAMO-CEREBELLAR FUNCTIONAL CONNECTIVITY IN PREMANIFEST HUNTINGTON'S DISEASE.

Melanie A Morrison, Jingwen Yao, Radhika Bhalerao

    Medrxiv : the Preprint Server for Health Sciences
    |January 27, 2025
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    Summary

    Transient changes in thalamo-cerebellar connectivity occur in premanifest Huntington's disease (HD). These findings suggest potential biomarkers for tracking disease progression and developing new therapeutic strategies for this neurodegenerative condition.

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    Area of Science:

    • Neuroscience
    • Genetics
    • Medical Imaging

    Background:

    • Huntington's disease (HD) is a fatal genetic neurodegenerative disorder with no current disease-modifying therapies.
    • Understanding HD progression mechanisms is crucial for developing new management strategies.
    • Aberrant thalamo-cortical and striato-cerebellar circuitry changes are observed in early stages of HD.

    Purpose of the Study:

    • To investigate the relationship between thalamo-cerebellar connectivity and the progression of Huntington's disease.
    • To identify potential imaging biomarkers for HD progression.

    Main Methods:

    • Utilized prospective and retrospective data from single-center (n=34) and public TRACK-HD (n=91) cohorts.
    • Employed 3T and 7T MRI to assess thalamo-cerebellar connectivity.
    • Correlated connectivity metrics with motor scores, cognitive performance, and predicted years to symptom onset.

    Main Results:

    • Significant differences in thalamo-dentate connectivity were found between premanifest HD patients and controls (p < 0.05).
    • Thalamic connectivity correlated with years to onset and cognitive performance, indicating transient functional alterations in premanifest HD.
    • Connectivity patterns varied based on motor scores in the premanifest TRACK-HD cohort.

    Conclusions:

    • Transient alterations in thalamo-cerebellar connectivity are observed in premanifest Huntington's disease, changing with disease progression.
    • These connectivity changes may serve as a potential biomarker for HD progression.
    • Further research is needed to validate these findings and their clinical utility.