Progressive supranuclear palsy (PSP), named also Steele-Richardson-Olszewski disease, is a neurodegenerative disorder characterized clinically by supranuclear ophthalmoplegia, pseudobulbar palsy, parkinsonism and axial dystonia. Dementia is also a common feature at the end-stage of the disease.
Key words: postural instability, frontal cognitive dysfunction, slowing of saccades
Prevalence: 6.4/100.000; >75% undiagnosed
Incidence: 5.4 new cases per 100.000 person/year
Neuropathologically, PSP is characterized by neuronal loss, gliosis and NFT. NFT were first described in basal ganglia, brain stem, and cerebellum (Steele et al., 1964). The subcortical localization of the neuropathological lesions has led to the definition of PSP as a model of "subcortical dementias" (Albert 1978; Cummings and Benson, 1984). More recently, a cortical involvement of the degenerating process has been described, with the same features as subcortical NFT (Hof et al., 1992a ; Hauw et al., 1990). These studies demonstrated that the primary motor cortex is more severely affected than isocortical association areas compared to AD (Hauw et al., 1990; Hof et al., 1992a). Preliminary neuropathologic criteria for the diagnosis of PSP have been defined (Hauw et al., 1994).
Immunohistochemical studies have revealed that NFT are denser in supragranular layers (III) than in infragranular layers (V) in PSP, while in AD, NFT are denser in layer V than in layer III. Neurofibrillary tangles are found in many subcortical nuclei as well as in the isocortex, especially in the primary motor region (Brodmann area 4) (Hauw et al., 1990; Hof et al., 1992a).
Ultrastructural analyses further support difference between AD and PSP, since PHF are found in AD (Kidd, 1963) while straight filaments are observed in PSP (Tellez-Nagel and Wisniewski, 1973; Tomonaga, 1977).
At the biochemical level, the profile is a major doublet of aggregated tau proteins, tau 64 and 69 kDa (Flament et al, 1991). A minor Tau 74 kDa is present (Sergeant et al, 1998).
Tau lesions in PSP and CBD are exclusively composed of tau isoforms with exon 10 (Sergeant et al, 1999).
Therefore, Tau aggregates in PSP and CBD have a specific pattern (type II), different from Alzheimer's disease (type I) and from Pick's disease (Type III)
THE 3R AND 4R CLASSIFICATION
The upper tau doublet (64, 69), so characteristic, is found in subcortical and cortical areas at the last stage of the disease, when dementia is observed.
At the biochemical level, we were not able to distinguish between PSP and CBD: are they at th opposite ends of the same spectrum?
It is interesting to note that the presence of NFT in cortical areas is always correlated to dementia. We had the opportunity to analyze materials obtained from a non-demented very young (33-year-old) PSP patient. In this case, abnormally phosphorylated tau proteins were found in both basal ganglia and thalamus, whereas they were absent in all of the other areas studied including amygdala, hippocampus, and Brodmann's areas 4, 9, 11, 17, 18, 20 and 24. Conversely, the other PSP studied cases with dementia contained large amounts of pathological tau proteins in the neocortex especially in Brodmann areas 4 and 6 and in subcortical structures.