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中国社区尸检队列中的神经病理学合并症、遗传学与认知

Neuropathological comorbidity, genetics and cognition in a Chinese community-based autopsy cohort.

作者信息

Wu Wei, Wang Xue, Xu Yuanyuan, Ma Chao, Qian Xiaojing, Qiu Wenying

机构信息

Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, 100005, China.

National Human Brain Bank for Development and Function, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, China.

出版信息

Brain. 2025 Feb 4. doi: 10.1093/brain/awaf039.

Abstract

Neurodegenerative comorbidities are common and critical, yet data specific to the Chinese population remains limited. The study aims to investigate the prevalence and associations of neuropathologic changes and comorbidities, and their correlation with genetics and cognition in a community-dwelling autopsy cohort in China. Datasets of 610 participants were obtained from the National Human Brain Bank for Development and Function at the Chinese Academy of Medical Sciences/Peking Union Medical College. Neuropathological changes analysed included Alzheimer's disease neuropathological change (ADNC) (n = 331); α-synucleinopathies (n = 124) with 120 Lewy body disease (LBD) and 4 multiple system atrophy; limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC) (n = 341); primary age-related tauopathy (PART) (n = 231); argyrophilic grain disease (AGD) (n = 107); age-related tau astrogliopathy (ARTAG) (n = 144); cerebral amyloid angiopathy (CAA) (n = 183); hippocampus sclerosis (HS) (n = 46). Frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and amygdala-predominant LBD are rare. Descriptive statistics and logistic regression models were used to assess the neuropathological associations. Increased age at death was correlated with increased severity in ADNC, LBD, and LATE-NC, as well as with a higher number of comorbidities. APOE ε4 allele frequency in the present autopsy cohort was 13.63%. The presence of the APOE ε4 allele was linked to an advanced ADNC stage and increased comorbidities. The co-pathology prevalence varied by pathologies, with notable increases in specific subgroups: within the ADNC subgroups, LBD, LATE-NC, CAA, and HS were more frequent in advanced stages; in the LATE-NC subgroups, ADNC, CAA, and ARTAG increased, while PART decreased in higher LATE-NC stages. PART cases presented the highest proportion of pure pathology (37.2%) compared to other groups. Advanced ADNC stages were significantly associated with higher LATE-NC stages, and vice versa. Neocortical LBD was correlated with elevated ADNC levels, and higher LATE-NC stages were associated with worsening LBD pathology. High level ADNC, neocortical LBD, and stage 3 of LATE-NC were identified as independent predictors of severe cognition status. Our study suggests that older age at death and APOE ε4 presence are the risk factors for neuropathologic comorbidities in Chinese people. The findings underscore the importance of considering comorbid neurologic diagnoses and therapies in clinical practice.

摘要

神经退行性共病很常见且很关键,但针对中国人群的具体数据仍然有限。本研究旨在调查中国一个社区尸检队列中神经病理变化和共病的患病率及关联,以及它们与遗传学和认知的相关性。610名参与者的数据集来自中国医学科学院/北京协和医学院国家人类脑发育与功能脑库。分析的神经病理变化包括阿尔茨海默病神经病理变化(ADNC)(n = 331);α-突触核蛋白病(n = 124),其中120例为路易体病(LBD),4例为多系统萎缩;边缘叶为主的年龄相关性TDP-43脑病神经病理变化(LATE-NC)(n = 341);原发性年龄相关性tau病(PART)(n = 231);嗜银颗粒病(AGD)(n = 107);年龄相关性tau星形胶质细胞病(ARTAG)(n = 144);脑淀粉样血管病(CAA)(n = 183);海马硬化(HS)(n = 46)。额颞叶变性、肌萎缩侧索硬化和杏仁核为主的LBD很少见。采用描述性统计和逻辑回归模型来评估神经病理关联。死亡年龄增加与ADNC、LBD和LATE-NC严重程度增加以及共病数量增加相关。本尸检队列中APOE ε4等位基因频率为13.63%。APOE ε4等位基因的存在与ADNC晚期阶段和共病增加有关。共病理患病率因病理类型而异,特定亚组有显著增加:在ADNC亚组中,LBD、LATE-NC、CAA和HS在晚期更常见;在LATE-NC亚组中,ADNC、CAA和ARTAG增加,而PART在LATE-NC较高阶段减少。与其他组相比,PART病例的纯病理比例最高(37.2%)。ADNC晚期阶段与LATE-NC较高阶段显著相关,反之亦然。新皮质LBD与ADNC水平升高相关,LATE-NC较高阶段与LBD病理恶化相关。高水平ADNC、新皮质LBD和LATE-NC 3期被确定为严重认知状态的独立预测因素。我们的研究表明,死亡年龄较大和存在APOE ε4是中国人神经病理共病的危险因素。这些发现强调了在临床实践中考虑共病神经诊断和治疗的重要性。

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