Summary
Progressive supranuclear palsy (PSP or Steele-Richardson-Olszewski disease) is a rare, late-onset (sixth decade) neurodegenerative disease. It is characterized by its clinical features (e.g., parkinsonism, postural instability, supranuclear gaze palsy), type and distribution of the pathology (e.g., tau-immunoreactive tangles in specific brainstem areas, basal ganglia, frontal neocortex), deficits in several neurotransmitter systems (e.g., dopaminergic, cholinergic, gabaergic), and abnormalities in the patterns of tau isoforms. The behavioral manifestations may also include language disturbances and frontal-lobe-type behavior. Neuropathologically, PSP is characterized by neuronal loss, gliosis with astrocytic plaques and neurofibrillary tangles in the affected brain areas. Biochemically, the tauopathy is composed of a preponderance of four-repeat (exon 10 positive) tau isoforms, named 4R tauopathy, and a characteristic biochemical profile (doublet tau 64 and tau 69). The tauopathy extends progressively along neuron-to-neuron connections from the brain stem to the striatum, then the frontal motor area, and later to most other neocortical areas. The H1H1 haplotype of the tau gene is a risk factor for this disease. A therapeutical trial at the European level is ongoing. *Author: Dr A. Delacourte (February 2005)*.
