Wang Jie, Huang Qi, Chen Xing, You Zhiwen, He Kun, Guo Qihao, Huang Yiyun, Yang Yang, Lin Zengping, Guo Tengfei, Zhao Jun, Guan Yihui, Li Binyin, Xie Fang
Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Department of Nuclear Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 310000, China.
Mol Psychiatry. 2024 Sep;29(9):2799-2809. doi: 10.1038/s41380-024-02501-z. Epub 2024 Apr 8.
The associations of synaptic loss with amyloid-β (Aβ) and tau pathology measured by positron emission tomography (PET) and plasma analysis in Alzheimer's disease (AD) patients are unknown. Seventy-five participants, including 26 AD patients, 19 mild cognitive impairment (MCI) patients, and 30 normal controls (NCs), underwent [F]SynVesT-1 PET/MR scans to assess synaptic density and [F]florbetapir and [F]MK6240 PET/CT scans to evaluate Aβ plaques and tau tangles. Among them, 19 AD patients, 12 MCI patients, and 29 NCs had plasma Aβ42/40 and p-tau181 levels measured by the Simoa platform. Twenty-three individuals, 6 AD patients, 4 MCI patients, and 13 NCs, underwent [F]SynVesT-1 PET/MRI and [F]MK6240 PET/CT scans during a one-year follow-up assessment. The associations of Aβ and tau pathology with cross-sectional and longitudinal synaptic loss were investigated using Pearson correlation analyses, generalized linear models and mediation analyses. AD patients exhibited lower synaptic density than NCs and MCI patients. In the whole cohort, global Aβ deposition was associated with synaptic loss in the medial (r = -0.431, p < 0.001) and lateral (r = -0.406, p < 0.001) temporal lobes. Synaptic density in almost all regions was related to the corresponding regional tau tangles independent of global Aβ deposition in the whole cohort and stratified groups. Synaptic density in the medial and lateral temporal lobes was correlated with plasma Aβ42/40 (r = 0.300, p = 0.020/r = 0.289, p = 0.025) and plasma p-tau 181 (r = -0.412, p = 0.001/r = -0.529, p < 0.001) levels in the whole cohort. Mediation analyses revealed that tau tangles mediated the relationship between Aβ plaques and synaptic density in the whole cohort. Baseline tau pathology was positively associated with longitudinal synaptic loss. This study suggested that tau burden is strongly linked to synaptic density independent of Aβ plaques, and also can predict longitudinal synaptic loss.
在阿尔茨海默病（AD）患者中，通过正电子发射断层扫描（PET）和血浆分析测量的突触丧失与淀粉样β蛋白（Aβ）和tau病理之间的关联尚不清楚。75名参与者，包括26名AD患者、19名轻度认知障碍（MCI）患者和30名正常对照（NC），接受了[F]SynVesT-1 PET/MR扫描以评估突触密度，以及[F]florbetapir和[F]MK6240 PET/CT扫描以评估Aβ斑块和tau缠结。其中，19名AD患者、12名MCI患者和29名NC通过Simoa平台测量了血浆Aβ42/40和p-tau181水平。23名个体，6名AD患者、4名MCI患者和13名NC，在为期一年的随访评估期间接受了[F]SynVesT-1 PET/MRI和[F]MK6240 PET/CT扫描。使用Pearson相关分析、广义线性模型和中介分析研究了Aβ和tau病理与横断面和纵向突触丧失之间的关联。AD患者的突触密度低于NC和MCI患者。在整个队列中，全球Aβ沉积与内侧（r = -0.431，p < 0.001）和外侧（r = -0.406，p < 0.001）颞叶的突触丧失相关。在整个队列和分层组中，几乎所有区域的突触密度都与相应区域的tau缠结相关，而与全球Aβ沉积无关。内侧和外侧颞叶的突触密度与整个队列中的血浆Aβ42/40（r = 0.300，p = 0.020/r = 0.289，p = 0.025）和血浆p-tau 181（r = -0.412，p = 0.001/r = -0.529，p < 0.001）水平相关。中介分析表明，tau缠结介导了整个队列中Aβ斑块与突触密度之间的关系。基线tau病理与纵向突触丧失呈正相关。这项研究表明，tau负荷与突触密度密切相关，与Aβ斑块无关，并且还可以预测纵向突触丧失。
