Phosphorylated TDP-43 Staging of Primary Age-Related Tauopathy

• Published in: Neuroscience bulletin Vol. 35; no. 2; pp. 183 - 192
• Main Authors: Zhang, Xiaoling, Sun, Bing, Wang, Xing, Lu, Hui, Shao, Fangjie, Rozemuller, Annemieke J. M., Liang, Huazheng, Liu, Chong, Chen, Jiadong, Huang, Manli, Zhu, Keqing
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 02-04-2019; Springer
• Subjects: Advertising executives; Aged; Aged, 80 and over; Aging - metabolism; Aging - pathology; Alzheimer's disease; Anatomy; Anesthesiology; Biomedical and Life Sciences; Biomedicine; Brain; Brain - metabolism; Brain - pathology; Disease Progression; DNA-Binding Proteins - metabolism; Female; Human Physiology; Humans; Immunohistochemistry; Inclusion Bodies - pathology; Male; Medical research; Medicine, Experimental; Middle Aged; Neurofibrillary Tangles - metabolism; Neurofibrillary Tangles - pathology; Neurology; Neurons - metabolism; Neurons - pathology; Neurosciences; Original; Original Article; Pain Medicine; Protein binding; Severity of Illness Index; Tauopathies - metabolism; Tauopathies - pathology; Alzheimer’s disease; Primary age-related tauopathy; Neurofibrillary tangle; TDP-43; Hippocampus
• ISSN: 1673-7067; 1995-8218
• DOI: 10.1007/s12264-018-0300-0

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.