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Distribution and characteristics of transactive response DNA binding protein 43 kDa pathology in progressive supranuclear palsy
Author(s) -
Koga Shunsuke,
SanchezContreras Monica,
Josephs Keith A.,
Uitti Ryan J.,
GraffRadford Neill,
Gerpen Jay A.,
Cheshire William P.,
Wszolek Zbigniew K.,
Rademakers Rosa,
Dickson Dennis W.
Publication year - 2017
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.26809
Subject(s) - hippocampus , entorhinal cortex , transactive memory , progressive supranuclear palsy , hippocampal sclerosis , hippocampal formation , pathology , amygdala , temporal lobe , alzheimer's disease , psychology , disease , neuroscience , medicine , epilepsy , cognitive psychology
Background This study aimed to determine the frequency of transactive response DNA binding protein 43 kDa pathology in PSP, the clinical features of patients with this pathology, and genetic risk factors for it. Methods Hippocampal sections were screened with immunohistochemistry for transactive response DNA binding protein 43 kDa in 945 PSP cases. A subset of 261 cases that were negative in hippocampus was screened in the amygdala. The density and disruption of this pathology, as well as regional tau burden, and clinical and genetic characteristics were analyzed. Results We observed transactive response DNA binding protein 43 kDa pathology in 47 cases in the hippocampus and an additional 9 cases that only affected the amygdala. Hippocampal sclerosis was the strongest risk factor, followed by Alzheimer's disease pathology, argyrophilic grain disease, and older age at death. Five stages of transactive response DNA binding protein 43 kDa pathology were identified in PSP: Stage A had pathology only in the amygdala (16%); stage I had pathology confined to the hippocampus and entorhinal cortex (9%); stage II included both regions of stage A and I (38%); stage III spread further to medial occipitotemporal gyrus (20%); and stage IV had pathology in the dorsolateral frontal lobe (18%). Anatomical areas vulnerable to PSP pathology had varying degrees of this pathology in stage II and later. PSP with transactive response DNA binding protein 43 kDa pathology were older at disease onset and had lower median MMSE scores; however, the latter was driven by concurrent pathologies. Conclusions Distribution and clinical characteristics of transactive response DNA binding protein 43 kDa pathology in PSP were influenced by concurrent pathologies. This is the first study to observe that PSP‐vulnerable regions are also susceptible to this non‐tau pathology. © 2016 International Parkinson and Movement Disorder Society.