Phosphorylated TDP-43 Staging of Primary Age-Related Tauopathy
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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.
KeywordsTDP-43 Primary age-related tauopathy Alzheimer’s disease Neurofibrillary tangle Hippocampus
We thank the families of the patients who donated their brains to China Brain Bank in Zhejiang University School of Medicine and allowed the completion of this study. This work was supported by the National Science Foundation China (91632109 to JHZ, KQZ and HJH), the Zhejiang Provincial Natural Science Foundation (LY16H090013 to KQZ), and the Zhejiang Medical and Health Science and Technology Plan Project (WKJ2013-2-009 to KQZ).
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Conflict of interest
The authors declare that there is no conflict of interest.
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