Abstract for presentation at The Australian and New Zealand Association of Neurologists Annual Scientific Meeting 2007

Severity of tau deposition in progressive supranuclear palsy is associated with clinical phenotype

  • Dr David Williams, Faculty of Medicine (Neuroscience), Monash University (Alfred Hospital Campus), Australia
  • Dr Janice Holton, Reta Lila Weston Institute of Neurological Studies, United Kingdom
  • Kate Strand, Reta Lila Weston Institute of Neurological Studies, United Kingdom
  • Dr Alan Pittman, Reta Lila Weston Institute of Neurological Studies, United Kingdom
  • Dr Rohan de Silva, Reta Lila Weston Institute of Neurological Studies, United Kingdom
  • Prof Andrew Lees, Reta Lila Weston Institute of Neurological Studies, United Kingdom
  • Prof Tamas Revesz, Reta Lila Weston Institute of Neurological Studies, United Kingdom

    • Purpose: Variability of pathological tau in progressive supranuclear palsy (PSP) is reported, but no grading system has been established to account for it. Clinical syndromes associated with PSP-tau pathology now include PSP-Parkinsonism (PSP-P), in addition to classic Richardson’s syndrome (RS) and pure akinesia with gait freezing (PAGF). Regional variations in the types of tau lesions or differences in overall tau load may explain the clinical differences between these syndromes.
    Methods: Quantitative tau pathology assessment was performed in 17 brain regions in 42 cases of pathologically diagnosed PSP. Neurofibrillary tangles, tufted astrocytes, coiled bodies and thread pathology (CB+Th) were counted and a grading system was developed for each region. Using these grades the overall tau load was calculated in each case. To establish a simplified system for grading the severity of tau pathology, all data were explored to identify the minimum number of regions that satisfactorily summarised the overall tau severity. The repeatability of this grading system was tested.
    Results: The overall tau load was significantly higher in RS than in PSP-P (p=0.002). Using only the grade of CB+Th lesions in the SN, caudate and dentate nucleus, a reliable and repeatable 12 tiered grading system was established (PSP-tau score: 0 – least severe, 12 – most severe). PSP-tau score was negatively correlated with disease duration (Spearman’s rho -0.36p=0.028). The PSP-tau score in PSP-P (median 3, range 0-5) was significantly lower than in RS (5, 2-10, p<0.001). The weighted kappa for two independent pathologists using a visual aid for grading PSP-tau score was 0.71.
    Conclusions: We have identified significant pathological differences between the major clinical syndromes associated with PSP-tau pathology. The restricted, mild tau pathology in PSP-P supports its clinical distinction from RS. The grading system we have developed provides an easy-to-use and sensitive tool for the morphological assessment of PSP-tau pathology.

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