TY - JOUR
T1 - Copathology in Progressive Supranuclear Palsy
T2 - Does It Matter?
AU - Jecmenica Lukic, Milica
AU - Kurz, Carolin
AU - Respondek, Gesine
AU - Grau-Rivera, Oriol
AU - Compta, Yaroslau
AU - Gelpi, Ellen
AU - Troakes, Claire
AU - van Swieten, John C.
AU - Giese, Armin
AU - Roeber, Sigrun
AU - Arzberger, Thomas
AU - Höglinger, Günter
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Background: The influence of concomitant brain pathologies on the progression rate in PSP is unclear. Objectives: To analyze the frequency and severity of copathologies and their impact on the progression in PSP. Methods: We analyzed clinic-pathological features of 101 PSP patients. Diagnoses and stages of copathologies were established according to standardized criteria, including Alzheimer's disease–related pathology, argyrophilic grains, Lewy-related pathology, transactive response DNA-binding protein 43 pathology, fused in sarcoma pathology, cerebral amyloid angiopathy, and small vessel disease. Demographic data and major clinical milestones (frequency and latency to onset) were extracted from patients’ files. Results: Only 8% of 101 patients presented with pure PSP pathology without any copathology. Alzheimer's disease–related pathology was the most frequent (84%), followed by argyrophilic grains (58%), both occurring as single copathology or in combination with other proteinopathies or cerebrovascular disease. Lewy-related and transactive response DNA-binding protein 43 copathology occurred rarely (8% and 6%, respectively). Fused in sarcoma–positive cases were not found. While being common, copathology was mostly mild in severity, with the exception of frequently widespread argyrophilic grains. Small vessel disease was also frequent (65%). Cerebral amyloid angiopathy occurred only in the presence of Alzheimer's disease–related changes (25%). The copathologies did not have major impact on prevalence and time frame of major disease milestones. Conclusions: In PSP, concomitant neurodegenerative proteinopathies or cerebrovascular diseases are frequent, but generally mild in severity. Our data confirmed that four repeat tau is still the most relevant target for PSP, whereas the impact of copathologies on progression rate appears to be of less importance. This is relevant information for the development of disease-modifying therapies.
AB - Background: The influence of concomitant brain pathologies on the progression rate in PSP is unclear. Objectives: To analyze the frequency and severity of copathologies and their impact on the progression in PSP. Methods: We analyzed clinic-pathological features of 101 PSP patients. Diagnoses and stages of copathologies were established according to standardized criteria, including Alzheimer's disease–related pathology, argyrophilic grains, Lewy-related pathology, transactive response DNA-binding protein 43 pathology, fused in sarcoma pathology, cerebral amyloid angiopathy, and small vessel disease. Demographic data and major clinical milestones (frequency and latency to onset) were extracted from patients’ files. Results: Only 8% of 101 patients presented with pure PSP pathology without any copathology. Alzheimer's disease–related pathology was the most frequent (84%), followed by argyrophilic grains (58%), both occurring as single copathology or in combination with other proteinopathies or cerebrovascular disease. Lewy-related and transactive response DNA-binding protein 43 copathology occurred rarely (8% and 6%, respectively). Fused in sarcoma–positive cases were not found. While being common, copathology was mostly mild in severity, with the exception of frequently widespread argyrophilic grains. Small vessel disease was also frequent (65%). Cerebral amyloid angiopathy occurred only in the presence of Alzheimer's disease–related changes (25%). The copathologies did not have major impact on prevalence and time frame of major disease milestones. Conclusions: In PSP, concomitant neurodegenerative proteinopathies or cerebrovascular diseases are frequent, but generally mild in severity. Our data confirmed that four repeat tau is still the most relevant target for PSP, whereas the impact of copathologies on progression rate appears to be of less importance. This is relevant information for the development of disease-modifying therapies.
KW - clinic-pathological correlation
KW - clinical phenotype
KW - copathology
KW - progressive supranuclear palsy
UR - http://www.scopus.com/inward/record.url?scp=85080946350&partnerID=8YFLogxK
U2 - 10.1002/mds.28011
DO - 10.1002/mds.28011
M3 - Article
C2 - 32125724
AN - SCOPUS:85080946350
SN - 0885-3185
VL - 35
SP - 984
EP - 993
JO - Movement Disorders
JF - Movement Disorders
IS - 6
ER -
