Phosphorylated TDP-43 Staging of Primary Age-Related Tauopathy.
10.1007/s12264-018-0300-0
- Author:
Xiaoling ZHANG
1
;
Bing SUN
1
;
Xing WANG
2
;
Hui LU
1
;
Fangjie SHAO
2
;
Annemieke J M ROZEMULLER
3
;
Huazheng LIANG
4
;
Chong LIU
1
;
Jiadong CHEN
1
;
Manli HUANG
5
;
Keqing ZHU
6
Author Information
1. China Brain Bank and Department of Neurology in Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang Province, Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
2. Department of Pathology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
3. Department of Pathology, Amsterdam Neuroscience, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
4. Brain Structure and Function Group, Neuroscience Research Australia, Randwick, NSW, 2031, Australia.
5. Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
6. China Brain Bank and Department of Neurology in Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang Province, Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou, 310058, China. zhukeqing@zju.edu.cn.
- Publication Type:Journal Article
- Keywords:
Alzheimer’s disease;
Hippocampus;
Neurofibrillary tangle;
Primary age-related tauopathy;
TDP-43
- MeSH:
Aged;
Aged, 80 and over;
Aging;
metabolism;
pathology;
Brain;
metabolism;
pathology;
DNA-Binding Proteins;
metabolism;
Disease Progression;
Female;
Humans;
Immunohistochemistry;
Inclusion Bodies;
pathology;
Male;
Middle Aged;
Neurofibrillary Tangles;
metabolism;
pathology;
Neurons;
metabolism;
pathology;
Severity of Illness Index;
Tauopathies;
metabolism;
pathology
- From:
Neuroscience Bulletin
2019;35(2):183-192
- CountryChina
- Language:English
-
Abstract:
Primary age-related tauopathy (PART) is characterized by tau neurofibrillary tangles (NFTs) in the absence of amyloid plaque pathology. In the present study, we analyzed the distribution patterns of phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) in the brains of patients with PART. Immunohistochemistry and immunofluorescence double-labeling in multiple brain regions was performed on brain tissues from PART, Alzheimer's disease (AD), and aging control cases. We examined the regional distribution patterns of pTDP-43 intraneuronal inclusions in PART with Braak NFT stages > 0 and ≤ IV, and a Thal phase of 0 (no beta-amyloid present). We found four stages which indicated potentially sequential dissemination of pTDP-43 in PART. Stage I was characterized by the presence of pTDP-43 lesions in the amygdala, stage II by such lesions in the hippocampus, stage III by spread of pTDP-43 to the neocortex, and stage IV by pTDP-43 lesions in the putamen, pallidum, and insular cortex. In general, the distribution pattern of pTDP-43 pathology in PART cases was similar to the early TDP-43 stages reported in AD, but tended to be more restricted to the limbic system. However, there were some differences in the distribution patterns of pTDP-43 between PART and AD, especially in the dentate gyrus of the hippocampus. Positive correlations were found in PART between the Braak NFT stage and the pTDP-43 stage and density.
