Zhenxu Xiao1,2, Xue Wu3, Wanqing Wu1,2, Jingwei Yi3, Xiaoniu Liang1,2, Saineng Ding1,2, Li Zheng1,2, Jianfeng Luo4,5, Hongchen Gu3, Qianhua Zhao6,7, Hong Xu8, Ding Ding1,2. 1. Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Rd, Shanghai, China. 2. National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. 3. School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. 4. Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China. 5. Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, China. 6. Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Rd, Shanghai, China. qianhuazhao@fudan.edu.cn. 7. National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. qianhuazhao@fudan.edu.cn. 8. School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. xuhong@sjtu.edu.cn.
Abstract
BACKGROUND: Plasma biomarkers showed a promising value in the disease diagnosis and management of Alzheimer's disease (AD). However, profiles of the biomarkers and the associations with cognition across a spectrum of cognitive stages have seldom been reported. METHODS: We recruited 320 individuals with cognitive impairment and 131 cognitively normal participants from a memory clinic and a community cohort. Participants were classified into 6 groups based on their Clinical Dementia Rating (CDR) scores and clinical diagnosis, including AD, amnestic mild cognitive impairment (aMCI), and normal cognition (NC). A battery of neuropsychological tests was used to assess the global and domain-specific cognition. Plasma Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, total tau (t-tau), neurofilament protein light chain (NfL), and phosphorylated tau at threonine 181 (p-tau181) were quantified using the single-molecule array (Simoa) platform. RESULTS: All the plasma markers (Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, t-tau, NfL, p-tau181) showed certain discrepancies among NC, aMCI, and AD groups. The p-tau181 level showed a continuous escalating trend as the CDR scores increased from 0 (NC group) to 3 (severe AD). Compared with other biomarkers, p-tau181 had correlations with broader cognitive domains, covering global cognition (r = -0.536, P < 0.0001), memory (r = -0.481, P < 0.0001), attention (r = -0.437, P < 0.0001), visuospatial function (r = -0.385, P < 0.0001), and language (r = -0.177, P = 0.0003). Among participants with CDR ≥ 1, higher p-tau181 was correlated with worse global cognition (r = -0.301, P < 0.001). CONCLUSIONS: Plasma p-tau181 had correlations with broader cognitive domains, suggesting its potential as a promising clinical-relevant blood-based biomarker.
BACKGROUND: Plasma biomarkers showed a promising value in the disease diagnosis and management of Alzheimer's disease (AD). However, profiles of the biomarkers and the associations with cognition across a spectrum of cognitive stages have seldom been reported. METHODS: We recruited 320 individuals with cognitive impairment and 131 cognitively normal participants from a memory clinic and a community cohort. Participants were classified into 6 groups based on their Clinical Dementia Rating (CDR) scores and clinical diagnosis, including AD, amnestic mild cognitive impairment (aMCI), and normal cognition (NC). A battery of neuropsychological tests was used to assess the global and domain-specific cognition. Plasma Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, total tau (t-tau), neurofilament protein light chain (NfL), and phosphorylated tau at threonine 181 (p-tau181) were quantified using the single-molecule array (Simoa) platform. RESULTS: All the plasma markers (Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, t-tau, NfL, p-tau181) showed certain discrepancies among NC, aMCI, and AD groups. The p-tau181 level showed a continuous escalating trend as the CDR scores increased from 0 (NC group) to 3 (severe AD). Compared with other biomarkers, p-tau181 had correlations with broader cognitive domains, covering global cognition (r = -0.536, P < 0.0001), memory (r = -0.481, P < 0.0001), attention (r = -0.437, P < 0.0001), visuospatial function (r = -0.385, P < 0.0001), and language (r = -0.177, P = 0.0003). Among participants with CDR ≥ 1, higher p-tau181 was correlated with worse global cognition (r = -0.301, P < 0.001). CONCLUSIONS: Plasma p-tau181 had correlations with broader cognitive domains, suggesting its potential as a promising clinical-relevant blood-based biomarker.
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