Hao Xiaoli, Xiao Xuewen, Weng Ling, Lin Zhuojie, Xu Qian, Du Juan, Yang Qijie, Zhu Yuan, Liu Yiliang, Xu Tianyan, Zhou Yafang, Liao Xinxin, Guo Jifeng, Luo Shilin, Wang Junling, Yan Xinxiang, Tang Beisha, Li Jinchen, Jiao Bin, Shen Lu
Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
NPJ Parkinsons Dis. 2025 May 15;11(1):128. doi: 10.1038/s41531-025-00988-z.
Genetic investigations and associations with plasma biomarkers of dementia with Lewy bodies (DLB) in East Asian populations are lacking. The aim of our study is to identify candidate pathogenic variants and assess the diagnostic performance of plasma biomarkers among DLB patients in the Chinese population. This cohort included 151 DLB patients and 2010 controls, all of whom underwent whole genome sequencing. Plasma glial fibrillary acidic protein (GFAP), α-synuclein(αSyn), neurofilament light (NfL), and phosphorylated tau 217 (p-tau217) were detected in a subgroup. As a result, the APOE ε4 allele significantly increased DLB risk (p = 1.84E-11), while rare missense variants of USP13 gene were first found to be suggestively associated with DLB risk (p = 1.31E-5). Higher levels of plasma GFAP, αSyn, NfL, and p-tau217 were detected in DLB patients compared to controls (p < 0.001), which combined with polygenic risk scores (PRS) achieving an AUC of 0.927 for DLB diagnosis. Besides, significant correlations were observed between PRS of DLB and age at onset, the cumulative incidence rate, as well as plasma GFAP levels. In conclusion, this is the first study to simultaneously investigate the genetics and plasma biomarkers of DLB, highlighting the discriminative ability for DLB using PRS and plasma biomarker assay.
东亚人群中关于路易体痴呆（DLB）的基因研究以及与血浆生物标志物的关联尚属空白。我们研究的目的是在中国人群的DLB患者中识别候选致病变异，并评估血浆生物标志物的诊断性能。该队列包括151例DLB患者和2010例对照，所有参与者均接受了全基因组测序。在一个亚组中检测了血浆胶质纤维酸性蛋白（GFAP）、α-突触核蛋白（αSyn）、神经丝轻链（NfL）和磷酸化tau217（p-tau217）。结果显示，APOE ε4等位基因显著增加了DLB风险（p = 1.84E-11），而首次发现USP13基因的罕见错义变异与DLB风险存在提示性关联（p = 1.31E-5）。与对照组相比，DLB患者血浆GFAP、αSyn、NfL和p-tau217水平更高（p < 0.001），将这些指标与多基因风险评分（PRS）相结合，DLB诊断的曲线下面积（AUC）达到0.927。此外，还观察到DLB的PRS与发病年龄、累积发病率以及血浆GFAP水平之间存在显著相关性。总之，这是第一项同时研究DLB的遗传学和血浆生物标志物的研究，突出了使用PRS和血浆生物标志物检测对DLB的鉴别能力。
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