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Is the Phenotype Designation by PSP-MDS Criteria Stable Throughout the Disease Course and Consistent With Tau
Javier Sánchez-Ruiz de Gordoa1,2, Victoria Zelaya3, Paula Tellechea-Aramburo1
1Department of Neurology, Hospital Universitario de Navarra, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
Introduction:
The MDS-PSP criteria have shown high sensitivity for the PSP diagnosis, but do not discriminate the phenotype diversity. Our purpose was to search for anatomopathological differences among PSP phenotypes resulting from the application of the MDS-PSP criteria comparing with the previous ones.
Methods:
Thirty-four PSP cases from a single brain bank were retrospectively classified according to the criteria used by Respondek et al. in 2014 and the PSP-MDS criteria at 3 years (MDS-3y), 6 years (MDS-6y) and at the last clinical evaluation before death (MDS-last). Semiquantitative measurement of total, cortical and subcortical tau load was compared. For comparative analysis, PSP-Richardson syndrome and PSP postural instability were grouped (PSP-RS/PI) as well as the PSP atypical cortical phenotypes (PSP-Cx).
Results:
Applying the Respondek's criteria, PSP phenotypes were distributed as follow: 55.9% PSP-RS/PI, 26.5% PSP-Cx, 11.8% PSP-Parkinsonism (PSP-P), and 5.9% PSP-Cerebellum. PSP-RS/PI and PSP-Cx had a higher total tau load than PSP-P; PSP-Cx showed a higher cortical tau load than PSP-RS/PI and PSP-P; and PSP-RS/PI had a higher subcortical tau load than PSP-P. Applying the MDS-3y, MDS-6y and MDS-last criteria; the PSP-RS/PI group increased (67.6, 70.6 and 70.6% respectively) whereas the PSP-Cx group decreased (8.8, and 8.8 and 11.8%). Then, only differences in total and subcortical tau burden between PSP-RS/PI and PSP-P were observed.
Interpretation:
After the retrospective application of the new MDS-PSP criteria, total and subcortical tau load is higher in PSP-RS/PI than in PSP-P whereas no other differences in tau load between phenotypes were found, as a consequence of the loss of phenotypic diversity.
Insights
The new MDS-PSP criteria reduce the diversity of progressive supranuclear palsy phenotypes. This leads to higher total and subcortical tau loads in PSP-RS/PI compared to PSP-P, obscuring other differences.
Area of Science:
- Neuroscience
- Neuropathology
- Clinical Neurology
Background:
- The Movement Disorder Society-Progressive Supranuclear Palsy (MDS-PSP) criteria are sensitive for PSP diagnosis but lack phenotypic discrimination.
- Understanding anatomopathological differences across PSP phenotypes is crucial for accurate diagnosis and treatment.
Purpose of the Study:
- To investigate anatomopathological differences among progressive supranuclear palsy (PSP) phenotypes using the MDS-PSP criteria.
- To compare the diagnostic utility of the MDS-PSP criteria with previous classification methods.
Main Methods:
- Retrospective classification of 34 PSP cases using Respondek et al. (2014) criteria and MDS-PSP criteria at different time points (MDS-3y, MDS-6y, MDS-last).
- Semiquantitative measurement of total, cortical, and subcortical tau load.
- Grouping of PSP-Richardson syndrome/PSP postural instability (PSP-RS/PI) and atypical cortical phenotypes (PSP-Cx) for comparative analysis.
Main Results:
- The MDS-PSP criteria resulted in an increased proportion of PSP-RS/PI and a decreased proportion of PSP-Cx compared to Respondek's criteria.
- PSP-RS/PI and PSP-Cx exhibited higher total tau load than PSP-Parkinsonism (PSP-P) under Respondek's criteria.
- PSP-Cx showed higher cortical tau load than PSP-RS/PI and PSP-P; PSP-RS/PI had higher subcortical tau load than PSP-P.
Conclusions:
- The application of MDS-PSP criteria led to a loss of phenotypic diversity.
- Under MDS-PSP criteria, only differences in total and subcortical tau burden between PSP-RS/PI and PSP-P were observed.
- The study highlights the impact of diagnostic criteria on neuropathological findings in PSP phenotypes.
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