Abstract：
UNASSIGNED: Synaptic dysfunction is closely associated with cognitive function in Alzheimer\'s disease (AD), and is present already in an early stage of the disease.
UNASSIGNED: Using serial cerebrospinal fluid (CSF) sampling, we aimed to investigate slopes of CSF synaptic proteins, and their relation with cognition along the AD continuum.
UNASSIGNED: We included subjects with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) (n = 50 amyloid-β+ [A +], n = 50 A-) and 50 patients with AD dementia from the Amsterdam dementia cohort, with CSF at two time points (median[IQR] 2.1[1.4-2.7] years). We analyzed 17 synaptic proteins and neurofilament light (NfL). Using linear mixed models we assessed trajectories of protein levels, and associations with cognitive decline (repeated Mini-Mental State Examination). We used Cox regression models to assess predictive value of protein levels for progression to AD dementia.
UNASSIGNED: At baseline most proteins showed increased levels in AD dementia compared to the other groups. In contrast NPTX2 levels were lower in AD dementia. Higher baseline levels of SNAP25, β-syn, and 14-3-3 proteins were associated with faster cognitive decline (St.B[SE] -0.27[0.12] to -0.61[0.12]). Longitudinal analyses showed that SYT1 and NPTX levels decreased over time in AD dementia (st.B[SE] -0.10[0.04] to -0.15[0.05]) and SCD/MCI-A+ (St.B[SE] -0.07[0.03] to -0.12[0.03]), but not in SCD/MCI-A- (pinteraction < 0.05). Increase over time in NfL levels was associated with faster cognitive decline in AD dementia (St.B[SE] -1.75[0.58]), but not in the other groups (pinteraction < 0.05).
UNASSIGNED: CSF synaptic proteins showed different slopes over time, suggesting complex synaptic dynamics. High levels of especially SNAP-25 may have value for prediction of cognitive decline in early AD stages, while increase in NfL over time correlates better with cognitive decline in later stages.
UNASSIGNED: Using serial cerebrospinal fluid (CSF) sampling, we aimed to investigate slopes of CSF synaptic proteins, and their relation with cognition along the AD continuum.
UNASSIGNED: We included subjects with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) (n = 50 amyloid-β+ [A +], n = 50 A-) and 50 patients with AD dementia from the Amsterdam dementia cohort, with CSF at two time points (median[IQR] 2.1[1.4-2.7] years). We analyzed 17 synaptic proteins and neurofilament light (NfL). Using linear mixed models we assessed trajectories of protein levels, and associations with cognitive decline (repeated Mini-Mental State Examination). We used Cox regression models to assess predictive value of protein levels for progression to AD dementia.
UNASSIGNED: At baseline most proteins showed increased levels in AD dementia compared to the other groups. In contrast NPTX2 levels were lower in AD dementia. Higher baseline levels of SNAP25, β-syn, and 14-3-3 proteins were associated with faster cognitive decline (St.B[SE] -0.27[0.12] to -0.61[0.12]). Longitudinal analyses showed that SYT1 and NPTX levels decreased over time in AD dementia (st.B[SE] -0.10[0.04] to -0.15[0.05]) and SCD/MCI-A+ (St.B[SE] -0.07[0.03] to -0.12[0.03]), but not in SCD/MCI-A- (pinteraction < 0.05). Increase over time in NfL levels was associated with faster cognitive decline in AD dementia (St.B[SE] -1.75[0.58]), but not in the other groups (pinteraction < 0.05).
UNASSIGNED: CSF synaptic proteins showed different slopes over time, suggesting complex synaptic dynamics. High levels of especially SNAP-25 may have value for prediction of cognitive decline in early AD stages, while increase in NfL over time correlates better with cognitive decline in later stages.
摘要：
■突触功能障碍与阿尔茨海默病（AD）的认知功能密切相关，并且已经存在于疾病的早期阶段。
■使用连续脑脊液（CSF）采样，我们的目的是研究脑脊液突触蛋白的斜率，以及它们与AD连续体认知的关系。
■我们纳入了主观性认知功能减退（SCD）或轻度认知障碍（MCI）的受试者（n=50淀粉样蛋白-β[A]，n=50A-）和阿姆斯特丹痴呆症队列中的50例AD痴呆症患者，CSF在两个时间点（中位数[IQR]2.1[1.4-2.7]年）。我们分析了17种突触蛋白和神经丝光（NfL）。使用线性混合模型，我们评估了蛋白质水平的轨迹，以及与认知能力下降的关联（重复的迷你精神状态检查）。我们使用Cox回归模型来评估蛋白质水平对AD痴呆进展的预测价值。
■在基线时，与其他组相比，大多数蛋白质在AD痴呆中显示出升高的水平。相反,在AD痴呆中NPTX2水平较低。更高的基线水平的SNAP25，β-syn，和14-3-3蛋白与更快的认知下降相关（St.B[SE]-0.27[0.12]至-0.61[0.12]）。纵向分析表明，AD痴呆患者的SYT1和NPTX水平随时间降低（st。B[SE]-0.10[0.04]至-0.15[0.05]）和SCD/MCI-A+（St.B[SE]-0.07[0.03]至-0.12[0.03]），但在SCD/MCI-A-中没有（p相互作用<0.05）。随着时间的推移，NfL水平的增加与AD痴呆的认知下降速度加快相关（St.B[SE]-1.75[0.58]），但在其他组中没有（pinteraction<0.05）。
■CSF突触蛋白随着时间的推移显示出不同的斜率，暗示了复杂的突触动力学.高水平尤其是SNAP-25可能对AD早期认知功能下降有预测价值。而随着时间的推移，NfL的增加与后期认知能力下降的相关性更好。
■使用连续脑脊液（CSF）采样，我们的目的是研究脑脊液突触蛋白的斜率，以及它们与AD连续体认知的关系。
■我们纳入了主观性认知功能减退（SCD）或轻度认知障碍（MCI）的受试者（n=50淀粉样蛋白-β[A]，n=50A-）和阿姆斯特丹痴呆症队列中的50例AD痴呆症患者，CSF在两个时间点（中位数[IQR]2.1[1.4-2.7]年）。我们分析了17种突触蛋白和神经丝光（NfL）。使用线性混合模型，我们评估了蛋白质水平的轨迹，以及与认知能力下降的关联（重复的迷你精神状态检查）。我们使用Cox回归模型来评估蛋白质水平对AD痴呆进展的预测价值。
■在基线时，与其他组相比，大多数蛋白质在AD痴呆中显示出升高的水平。相反,在AD痴呆中NPTX2水平较低。更高的基线水平的SNAP25，β-syn，和14-3-3蛋白与更快的认知下降相关（St.B[SE]-0.27[0.12]至-0.61[0.12]）。纵向分析表明，AD痴呆患者的SYT1和NPTX水平随时间降低（st。B[SE]-0.10[0.04]至-0.15[0.05]）和SCD/MCI-A+（St.B[SE]-0.07[0.03]至-0.12[0.03]），但在SCD/MCI-A-中没有（p相互作用<0.05）。随着时间的推移，NfL水平的增加与AD痴呆的认知下降速度加快相关（St.B[SE]-1.75[0.58]），但在其他组中没有（pinteraction<0.05）。
■CSF突触蛋白随着时间的推移显示出不同的斜率，暗示了复杂的突触动力学.高水平尤其是SNAP-25可能对AD早期认知功能下降有预测价值。而随着时间的推移，NfL的增加与后期认知能力下降的相关性更好。
