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 phosphorylated43-kDa ...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 phosphorylated43-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 B 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.展开更多
Primary age-related tauopathy(PART)is characterized by the presence of tau neurofibrillary tangles(NFTs)which are typically observed in Alzheimer’s disease(AD)brains,with few or withoutβ-amyloid(Aβ)plaques.The diag...Primary age-related tauopathy(PART)is characterized by the presence of tau neurofibrillary tangles(NFTs)which are typically observed in Alzheimer’s disease(AD)brains,with few or withoutβ-amyloid(Aβ)plaques.The diagnosis of PART can be categorized into“definite”or“possible”depending on the amount of Aβplaques.Definite PART is diagnosed when NFTs are observed and the Braak stage is≤IV,with Thal AβPhase 0(Crary et al.,2014).According to the neuropathological diagnostic criteria,we reported reported that PART was frequently observed in the Chinese population according to our findings from specimens in our brain bank,with 47%of brain bank subjects meeting the criteria for PART.There is no consensus on the nature of PART.It remains to be elucidated whether PART is an early form of AD or a novel tauopathy(Duyckaerts et al.,2015;Jellinger et al.,2015).展开更多
基金supported by the National Science Foundation China(91632109 to JHZ,KQZ and HJH)the Zhejiang Provincial Natural Science Foundation(LY16H090013 to KQZ)the Zhejiang Medical and Health Science and Technology Plan Project(WKJ20132-009 to KQZ)
文摘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 phosphorylated43-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 B 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.
基金Project supported by the National Natural Science Foundation of China(Nos.91632109 and 81971184)the Zhejiang Provincial Natural Science Foundation of China(No.LY16H090013)the Zhejiang Medical and Health Science and Technology Plan Project(No.WKJ2013-2-009),China.
文摘Primary age-related tauopathy(PART)is characterized by the presence of tau neurofibrillary tangles(NFTs)which are typically observed in Alzheimer’s disease(AD)brains,with few or withoutβ-amyloid(Aβ)plaques.The diagnosis of PART can be categorized into“definite”or“possible”depending on the amount of Aβplaques.Definite PART is diagnosed when NFTs are observed and the Braak stage is≤IV,with Thal AβPhase 0(Crary et al.,2014).According to the neuropathological diagnostic criteria,we reported reported that PART was frequently observed in the Chinese population according to our findings from specimens in our brain bank,with 47%of brain bank subjects meeting the criteria for PART.There is no consensus on the nature of PART.It remains to be elucidated whether PART is an early form of AD or a novel tauopathy(Duyckaerts et al.,2015;Jellinger et al.,2015).
