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Delineation of Early Changes in Cases with Progressive Supranuclear Palsy-Like Pathology. Astrocytes in Striatum are Primary Targets of Tau Phosphorylation and GFAP Oxidation

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Abstract

Progressive supranuclear palsy (PSP) is a complex tauopathy usually confirmed at post-mortem in advanced stages of the disease. Early PSP-like changes that may outline the course of the disease are not known. Since PSP is not rarely associated with argyrophilic grain disease (AGD) of varible intensity, the present study was focused on AGD cases with associated PSP-like changes in an attempt to delineate early PSP-like pathology in this category of cases. Three were typical clinical and pathological PSP. Another case presented with cognitive impairment, abnormal behavior and two falls in the last three months. One case suffered from mild cognitive impairment, and two had no evidence of neurological abnormality. Neuropathological study revealed, in addition to AGD, increased intensity and extent of lesion in three groups of regions, striatum, pallidus/subthalamus and selected nuclei of the brain stem, correlating with neurological impairment. Biochemical studies disclosed oxidative damage in the striatum and amygdala. Together the present observations suggest (i) early PSP-like lesions in the striatum, followed by the globus pallidus/subthalamus and selected nuclei of the brain stem; (ii) early involvement of neurons and astrocytes, but late appearance of tufted astrocytres; and (iii) oxidative damage of glial acidic protein in the striatum.
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Keywords: argyrophilic grain disease; glial fibrillary acidic protein oxidative damage; progressive supranuclear palsy

Document Type: Research Article

Publication date: April 1, 2009

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