Different tau pathology pattern in two clinical phenotypes of progressive supranuclear palsy.
BACKGROUND
The clinical and pathological heterogeneity of progressive supranuclear palsy (PSP) is well established. Recent clinicopathological studies showed much more severe and more widespread tau pathology in Richardson's syndrome (RS), clinically manifest by early onset, falls, supranuclear gaze palsy, dementia and shorter disease duration than in atypical PSP-parkinsonism (PSP-P) often mimicking Parkinson's disease, in which tau pathology is relatively restricted to substantia nigra, subthalamic nucleus and internal globus pallidus.


OBJECTIVE
To perform a comparative clinicopathological study of 30 autopsy-proven cases of PSP.


METHODS
Retrospective assessment of major clinical signs in 18 patients referred to as RS and 12 PSP-P, and semiquantitative assessment of the severity and distribution pattern of tau pathology in both phenotypes using routine stains and immunohistochemistry.


RESULTS
RS (61% males) and PSP-P (33% males) showed significant differences in clinical symptomatology and course (RS mean duration 4.2 years, PSP-P 13.8 years) and significant differences in histopathology: widespread tau pathology and related multisystem degeneration in RS and more restricted lesions in PSP-P, which, however, were not only involving predominantly the subthalamo-nigral-pallidal system. Cortical tau pathology in both groups was usually restricted to limbic areas, and neocortical Alzheimer-type pathology was only seen in very old or demented PSP patients.


CONCLUSIONS
The present study confirmed the recently reported existence of two distinct clinical phenotypes in patients with pathologically proven PSP-P and RS, showing significant differences in severity and distribution of tau pathology, the latter more severe and more widely distributed than in PSP-P.
Jellinger
Kurt A
KA
Institute of Clinical Neurobiology, Vienna, Austria. kurt.jellinger@univie.ac.at
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D005917:Globus Pallidus / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology; D010300:Parkinson Disease / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D013378:Substantia Nigra / Q000737:chemistry / Q000473:pathology; D020531:Subthalamic Nucleus / Q000737:chemistry / Q000473:pathology; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000032:analysis*
D016875:tau Proteins