Progressive supranuclear palsy (PSP) is one of the most common atypical Parkinsonian syndromes. Clinically, PSP is characterized by severe postural instability leading to falls, supranuclear gaze palsy, pseudobulbar palsy, axial rigidity, Parkinsonism and sometimes mild cognitive dysfunction (Steele et al., 1964; Litvan et al., 1996). Despite several attempts to the identification of genetic and biochemical markers, the early diagnosis among neurodegenerative extrapyramidal syndromes remains a clinical challenge. Pathologically, PSP is considered to be one of the tauopathies due to the presence of abnormally phosphorylated tau-protein in neurons and glia in subcortical and cortical structures. Unlike Parkinson's disease (PD), PSP is a tauopathy characterized, pathologically, by neuronal loss, granulovacuolar degeneration, gliosis and neurofibrillary tangles in the midbrain, pons and basal ganglia (Hauw et al., 1994). As to PSP most of the studies were performed in brain parenchyma revealing that the morphological (Berry et al., 2004) and biochemical characteristics (Arai et al., 2004) of tau aggregates are often similar to those observed in other diseases characterized by motor deficits, or dementia or both, i.e. corticobasal dementia
(CBD). Further, it has been already described that in both PSP and CBD the 4Rtau is mainly expressed. A large spectrum of neurodegenerative conditions is related to a disorder of Tau metabolism. In particular, Tau protein dysfunction has been recognised to play a crucial role in frontotemporal dementia (FTD) and other tauopathies, i.e. progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) (Hodges et al., 2004; Kertesz et al., 2005).
Several studies assessing cerebrospinal fluid (CSF) Tau levels have been performed in order to highlight a diversity of clinical and pathological findings. Notwithstanding, the results have been inconsistent so far. Some studies on FTD cases have found statistically increased levels of CSF Tau, whilst others have reported normal Tau concentrations (Grossman et al., 2005; Pijnenburg et al., 2004; Riemenschneider et al., 2002). In PSP and CBD syndrome (CBDS) patients, CSF Tau levels were found within normal range, though slightly increased in CBDS (Urakami et al., 2001). These data suggest that measurement of CSF total Tau does not properly describe Tau related-disorder heterogeneity, and therefore Tau is not an useful biomarker for their biological differential diagnosis. Recently, some authors have investigated the composition of cerebral Tau isoforms in autopsy confirmed-cases of PSP and CBD, to single out specific Tau processing leading to the different phenotypes. A Tau fragment resulting from the proteolytic metabolism of Tau has thus been identified, which allowed to differentiate
PSP from CBD (Arai et al., 2004). In PSP patients common MRI abnormalities comprise a reduction of the anteroposterior midbrain diameter, signal increase in
the midbrain, atrophy or signal increase of the red nucleus, frontal or temporal lobe atrophy and of the superior cerebellar peduncle (Schrag et al., 2000; Rizzo et al., 2008; Quattrone et al., 2008). On the basis of the pathological demonstration of superior cerebellar peduncle (SCP) atrophy in patients with PSP, Rizzo and colleagues recently found (2008) that diffusion weighted imaging (DWI) discriminated patients with PSP from PD and healthy subjects on the basis of SCP individual values. PSP patients showed in vivo microstructural features of cerebellar atrophy providing an additional support for early discrimination between PSP and other neurodegenerative parkinsonisms. However the neurophysiological features of such structural abnormalities have not deeply investigated.
(CBD). Further, it has been already described that in both PSP and CBD the 4Rtau is mainly expressed. A large spectrum of neurodegenerative conditions is related to a disorder of Tau metabolism. In particular, Tau protein dysfunction has been recognised to play a crucial role in frontotemporal dementia (FTD) and other tauopathies, i.e. progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) (Hodges et al., 2004; Kertesz et al., 2005).
Several studies assessing cerebrospinal fluid (CSF) Tau levels have been performed in order to highlight a diversity of clinical and pathological findings. Notwithstanding, the results have been inconsistent so far. Some studies on FTD cases have found statistically increased levels of CSF Tau, whilst others have reported normal Tau concentrations (Grossman et al., 2005; Pijnenburg et al., 2004; Riemenschneider et al., 2002). In PSP and CBD syndrome (CBDS) patients, CSF Tau levels were found within normal range, though slightly increased in CBDS (Urakami et al., 2001). These data suggest that measurement of CSF total Tau does not properly describe Tau related-disorder heterogeneity, and therefore Tau is not an useful biomarker for their biological differential diagnosis. Recently, some authors have investigated the composition of cerebral Tau isoforms in autopsy confirmed-cases of PSP and CBD, to single out specific Tau processing leading to the different phenotypes. A Tau fragment resulting from the proteolytic metabolism of Tau has thus been identified, which allowed to differentiate
PSP from CBD (Arai et al., 2004). In PSP patients common MRI abnormalities comprise a reduction of the anteroposterior midbrain diameter, signal increase in
the midbrain, atrophy or signal increase of the red nucleus, frontal or temporal lobe atrophy and of the superior cerebellar peduncle (Schrag et al., 2000; Rizzo et al., 2008; Quattrone et al., 2008). On the basis of the pathological demonstration of superior cerebellar peduncle (SCP) atrophy in patients with PSP, Rizzo and colleagues recently found (2008) that diffusion weighted imaging (DWI) discriminated patients with PSP from PD and healthy subjects on the basis of SCP individual values. PSP patients showed in vivo microstructural features of cerebellar atrophy providing an additional support for early discrimination between PSP and other neurodegenerative parkinsonisms. However the neurophysiological features of such structural abnormalities have not deeply investigated.