摘要
目的
分析中国人群中原发性衰老相关性tau 病(PART)的临床病理学特点,并比较其与老年性痴呆之间的差异.
创新点
PART 为新近提出的概念,其与老年性痴呆的关 系尚存在争论.目前未见针对中国人群PART 的 相关报道.本文首次报道了浙江大学医学院中国 人脑库中的PART 的临床病理学特点.
方法
回顾性分析相关病例,严格纳入标准.PART 在 中国人群中常见,50 岁以上人群占47%.平均年 龄(76±12)岁,女性14 例(30%),男性32 例 (70%).免疫组织化学法显示,按磷酸化tau 的Braak 分期,PART 大多为I 到Ш 期.异常蛋 白TDP43 和p62 在PART 中高表达,分别为67% 和70%; 在老年性痴呆中分别为83%和83%. TDP43 和p62 共表达在PART 为55%,在老年性 痴呆为79%.其中海马为PART 常见累及部位, TDP43 为61%,p62 为63%.仅4%的PART 患 者表现为轻度认知障碍.
结论
PART 在中国人群中常见; PART 大多无明显痴 呆症状; 异常蛋白TDP43 和p62 在PART 中高表 达,与老年性痴呆相比存在差异.
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References
Alafuzoff I, Ince PG, Arzberger T, et al., 2009. Staging/typing of Lewy body related α-synuclein pathology: a study of the BrainNet Europe Consortium. Acta Neuropathol, 117(6):635–652. https://doi.org/10.1007/s00401-009-0523-2.
Arnold SJ, Dugger BN, Beach TG, 2013. TDP-43 deposition in prospectively followed, cognitively normal elderly individuals: correlation with argyrophilic grains but not other concomitant pathologies. Acta Neuropathol, 126(1):51–57. https://doi.org/10.1007/s00401-013-1110-0
Bell WR, An Y, Kageyama Y, et al., 2019. Neuropathologic, genetic, and longitudinal cognitive profiles in primary age-related tauopathy (PART) and Alzheimer’s disease. Alzheimers Dement, 15(1):8–16. https://doi.org/10.1016/j.jalz.2018.07.215
Besser LM, Crary JF, Mock C, et al., 2017. Comparison of symptomatic and asymptomatic persons with primary age-related tauopathy. Neurology, 89(16):1707–1715. https://doi.org/10.1212/WNL.0000000000004521
Besser LM, Mock C, Teylan MA, et al., 2019. Differences in cognitive impairment in primary age-related tauopathy versus Alzheimer disease. J Neuropathol Exp Neurol, 78(3):219–228. https://doi.org/10.1093/jnen/nly132
Braak H, Thal DR, Ghebremedhin E, et al., 2011. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol, 70(11):960–969. https://doi.org/10.1097/NEN.0b013e318232a379
Crary JF, Trojanowski JQ, Schneider JA, et al., 2014. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol, 128(6):755–766. https://doi.org/10.1007/s00401-014-1349-0
Duyckaerts C, Braak H, Brion JP, et al., 2015. PART is part of Alzheimer disease. Acta Neuropathol, 129(5):749–756. https://doi.org/10.1007/s00401-015-1390-7
Elobeid A, Libard S, Leino M, et al., 2016. Altered proteins in the aging brain. J Neuropathol Exp Neurol, 75(4):316–325. https://doi.org/10.1093/jnen/nlw002
Jellinger KA, Alafuzoff I, Attems J, et al., 2015. PART, a distinct tauopathy, different from classical sporadic Alzheimer disease. Acta Neuropathol, 129(5):757–762. https://doi.org/10.1007/s00401-015-1407-2
Josephs KA, Murray ME, Whitwell JL, et al., 2016. Updated TDP-43 in Alzheimer’s disease staging scheme. Acta Neuropathol, 131(4):571–585. https://doi.org/10.1007/s00401-016-1537-1
Josephs KA, Murray ME, Tosakulwong N, et al., 2019. Brain atrophy in primary age-related tauopathy is linked to transactive response DNA-binding protein of 43 kDa. Alzheimers Dement, 15(6):799–806. https://doi.org/10.1016/j.jalz.2019.03.003
Kim D, Kim HS, Choi SM, et al., 2019. Primary age-related tauopathy (PART): an elderly brain pathology frequently encountered during autopsy. J Pathol Transl Med, 53(3):159–163. https://doi.org/10.4132/jptm.2019.03.14
Kovacs GG, Milenkovic I, Wöhrer A, et al., 2013. Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series. Acta Neuropathol, 126(3):365–384. https://doi.org/10.1007/s00401-013-1157-y
Kuusisto E, Salminen A, Alafuzoff I, 2002. Early accumulation of p62 in neurofibrillary tangles in Alzheimer’s disease: possible role in tangle formation. Neuropathol Appl Neurobiol, 28(3):228–237. https://doi.org/10.1046/j.1365-2990.2002.00394.x
Mikolaenko I, Pletnikova O, Kawas CH, et al., 2005. Alpha-synuclein lesions in normal aging, Parkinson disease, and Alzheimer disease: evidence from the Baltimore Longitudinal Study of Aging (BLSA). J Neuropathol Exp Neurol, 64(2):156–162. https://doi.org/10.1093/jnen/64.2.156
Nelson PT, Trojanowski JQ, Abner EL, et al., 2016. “New old pathologies”: AD, PART, and cerebral age-related TDP-43 with sclerosis (CARTS). J Neuropathol Exp Neurol, 75(6):482–498. https://doi.org/10.1093/jnen/nlw033
Nelson PT, Dickson DW, Trojanowski JQ, et al., 2019. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain, 142(6):1503–1527. https://doi.org/10.1093/brain/awz099
Tsartsalis S, Xekardaki A, Hof PR, et al., 2018. Early Alzheimer-type lesions in cognitively normal subjects. Neurobiol Aging, 62:34–44. https://doi.org/10.1016/j.neurobiolaging.2017.10.002
Uchino A, Takao M, Hatsuta H, et al., 2015. Incidence and extent of TDP-43 accumulation in aging human brain. Acta Neuropathol Commun, 3:35. https://doi.org/10.1186/s40478-015-0215-1
Zhang XL, Sun B, Wang X, et al., 2019. Phosphorylated TDP-43 staging of primary age-related tauopathy. Neurosci Bull, 35(2):183–192. https://doi.org/10.1007/s12264-018-0300-0
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We wish to thank the donors and their families for allowing the completion of this study.
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Xin WANG, Lei ZHANG, Juan-li WU, and Hui LU prepared the tissue for immunohistochemistry and performed statistical analysis. Ke-qing ZHU, Xin WANG, and Lei ZHANG contributed in the statistical assessment and data processing. Ke-qing ZHU designed the study, analyzed the results, and wrote the first version of the manuscript that was circulated among all the contributors for comments and suggestions. Hua-zheng LIANG, Chong LIU, Qing-qing TAO, and Zhi-ying WU contributed in the final version of the manuscript. All authors have read and approved the final manuscript. All authors have full access to all the data in the study and have responsibility for the integrity and security of the data.
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Table S1 Assessment of the altered protein expression
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Xin WANG, Lei ZHANG, Hui LU, Juan-li WU, Hua-zheng LIANG, Chong LIU, Qing-qing TAO, Zhi-ying WU, and Ke-qing ZHU declare that they have no conflict of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent was obtained from all patients for being included in the study.
Project supported by the National Natural Science Foundation of China (Nos. 91632109 and 81971184), the Zhejiang Provincial Natural Science Foundation of China (No. LY16H090013), and the Zhejiang Medical and Health Science and Technology Plan Project (No. WKJ2013-2-009), China
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Wang, X., Zhang, L., Lu, H. et al. Primary age-related tauopathy in a Chinese cohort. J. Zhejiang Univ. Sci. B 21, 256–262 (2020). https://doi.org/10.1631/jzus.B1900262
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DOI: https://doi.org/10.1631/jzus.B1900262