Bu Xian-Le, Zhu Wei, Wang Qing-Hua, Liu Zhuo-Ting, Bao Yun-Yu, Bai Yu-Di, Li Jiang-Hui, Liu Zhi-Hao, Zhao Jia-Ling, Xiang Yang, Jin Wang-Sheng, Wang Jun, Lei Xia, Wang Yan-Jiang
Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China.
Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, China.
Nat Commun. 2025 Jul 1;16(1):5905. doi: 10.1038/s41467-025-60748-8.
Multimorbidity is common in older adults. However, whether multimorbidity accelerates brain beta-amyloid (Aβ) deposition, the molecular driver of Alzheimer's disease (AD), in humans remains largely unknown. In this study, we selected 435 brain Aβ-positive participants with available longitudinal Aβ-PET data (mean duration 3.9 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Twenty-two self-reported chronic disorders were considered as a measure of the severity of multimorbidity. After adjustment for age, sex, education level, APOE-ε4 status and baseline cognitive state, individuals with a high or medium multimorbidity burden had faster rates of brain Aβ accumulation than individuals with a low multimorbidity burden. Moreover, both the central nervous system and peripheral system multimorbidity burdens were associated with longitudinal brain Aβ deposition. These results indicate that peripheral organ and tissue dysfunctions may contribute to AD pathogenesis, which may help researchers better understand AD pathogenesis and tailor interventions for AD from a systemic view.
多重疾病在老年人中很常见。然而，多重疾病是否会加速大脑β-淀粉样蛋白（Aβ）沉积（阿尔茨海默病（AD）的分子驱动因素）在人类中仍 largely unknown。在本研究中，我们从阿尔茨海默病神经影像倡议（ADNI）队列中选取了435名脑Aβ阳性且有可用纵向Aβ-PET数据（平均时长3.9年）的参与者。22种自我报告的慢性疾病被视为多重疾病严重程度的一种衡量指标。在对年龄、性别、教育水平、APOE-ε4状态和基线认知状态进行调整后，多重疾病负担高或中等的个体比多重疾病负担低的个体大脑Aβ积累速度更快。此外，中枢神经系统和外周系统的多重疾病负担均与纵向脑Aβ沉积相关。这些结果表明，外周器官和组织功能障碍可能促成AD发病机制，这可能有助于研究人员更好地理解AD发病机制，并从系统角度为AD量身定制干预措施。
