Publications by authors named "P T McColgan"

Article Synopsis
  • Therapeutic strategies to lower mutant huntingtin (mHTT) levels show promise in reversing Huntington's disease (HD) symptoms in animal models, highlighting the need for effective biomarkers to evaluate these therapies.
  • Neurofilament light chain (NfL) is a neurodegeneration biomarker that increases in the cerebrospinal fluid (CSF) and blood as HD progresses, but its role in assessing treatment efficacy remains unclear.
  • In studies with YAC128 mice, NfL levels were elevated compared to control mice, and while lowering mHTT before disease symptoms had minimal impact on plasma NfL, it led to a significant reduction in CSF NfL, especially when treatment was started after disease onset.
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The concentrations of neurofilament light chain (NfL) in cerebrospinal fluid (CSF) and plasma have become key biomarkers of many neurodegenerative diseases, including Huntington's Disease (HD). However, the relationship between the dynamics of NfL concentrations in CSF and the time-course of neurodegeneration (whole brain atrophy) has not yet been described in a quantitative and mechanistic manner. Here, we present a novel semi-mechanistic model, which postulates that the amount of NfL entering the CSF corresponds to the amount of NfL released from damaged neurons, whose degeneration results in a decrease in brain volume.

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Parkinson's disease is a common and debilitating neurodegenerative disorder, with over half of patients progressing to postural instability, dementia or death within 10 years of diagnosis. However, the onset and rate of progression to poor outcomes is highly variable, underpinned by heterogeneity in underlying pathological processes. Quantitative and sensitive measures predicting poor outcomes will be critical for targeted treatment, but most studies to date have been limited to a single modality or assessed patients with established cognitive impairment.

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