In:
Brain Communications, Oxford University Press (OUP)
Abstract:
Progressive supranuclear palsy is a neurodegenerative disease characterized by the deposition of four-repeat tau in neuronal and glial lesions in brainstem, cerebellar, subcortical, and cortical brain regions. There are varying clinical presentations of progressive supranuclear palsy with different neuroimaging signatures, presumed to be due to different topographical distributions and burden of tau. The classic Richardson syndrome presentation is considered a subcortical variant, while progressive supranuclear palsy with predominant speech and language impairment is considered a cortical variant, although the pathological underpinnings of these variants are unclear. In this case-control study we aimed to determine whether patterns of regional tau pathology differed between these variants, and whether tau burden correlated with neuroimaging. Thirty-three neuropathologically confirmed progressive supranuclear palsy patients with either the Richardson syndrome (n = 17) or speech/language (n = 16) variant, and antemortem MRI were included. Tau lesion burden was semiquantitatively graded in cerebellar, brainstem, subcortical, and cortical regions and combined to form neuronal and glial tau scores. Regional MRI volumes were converted to Z-scores using 33 age- and sex-matched controls. Diffusion tensor imaging metrics, including fractional anisotropy and mean diffusivity, were calculated. Tau burden and neuroimaging metrics were compared between groups and correlated using linear regression models. Neuronal and glial tau burden were higher in motor and superior frontal cortices in the speech/language variant. In subcortical and brainstem regions, only glial tau burden differed, with higher burden in globus pallidus, subthalamic nucleus, substantia nigra and red nucleus in Richardson's syndrome. No differences were observed in cerebellar dentate and striatum. Greater volume loss was observed in the motor cortex in the speech/language variant, and in the subthalamic nucleus, red nucleus, and midbrain in Richardson's syndrome. Fractional anisotropy was lower in midbrain and superior cerebellar peduncle in Richardson's syndrome. Mean diffusivity was greater in superior frontal cortex in the speech/language variant, and midbrain in Richardson's syndrome. Neuronal tau burden showed associations with volume loss, lower fractional anisotropy, and higher mean diffusivity in the superior frontal cortex, although these findings did not survive correction for multiple comparisons. Results suggest that a shift in the distribution of tau, particularly neuronal tau, within the progressive supranuclear palsy network of regions is driving different clinical presentations in progressive supranuclear palsy. The possibility of different disease epicenters in these clinical variants has potential implications for the use of imaging biomarkers in progressive supranuclear palsy.
Type of Medium:
Online Resource
ISSN:
2632-1297
DOI:
10.1093/braincomms/fcae113
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2024
detail.hit.zdb_id:
3020013-1
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