Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.
Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands.
J Alzheimers Dis. 2024;100(s1):S103-S114. doi: 10.3233/JAD-240610.
Synaptic dysfunction is closely associated with cognitive function in Alzheimer's disease (AD), and is present already in an early stage of the disease.
Using serial cerebrospinal fluid (CSF) sampling, we aimed to investigate slopes of CSF synaptic proteins, and their relation with cognition along the AD continuum.
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.
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).
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.
突触功能障碍与阿尔茨海默病（AD）的认知功能密切相关，并且在疾病的早期阶段就已经存在。
通过连续的脑脊液（CSF）采样，我们旨在研究 CSF 突触蛋白的斜率及其与 AD 连续体中认知的关系。
我们纳入了 50 名有主观认知下降（SCD）或轻度认知障碍（MCI）的受试者（Aβ+[n=50]，Aβ-[n=50]）和 50 名来自阿姆斯特丹痴呆队列的 AD 痴呆患者，他们的 CSF 采集时间间隔为 2.1 年（中位数[IQR]）。我们分析了 17 种突触蛋白和神经丝轻链（NfL）。使用线性混合模型评估蛋白质水平的轨迹，并评估与认知下降（重复使用简易精神状态检查）的关联。我们使用 Cox 回归模型评估蛋白质水平对进展为 AD 痴呆的预测价值。
在基线时，与其他组相比，AD 痴呆组的大多数蛋白质水平升高。相反，AD 痴呆组的 NPTX2 水平较低。较高的 SNAP25、β-syn 和 14-3-3 蛋白基线水平与认知下降速度较快有关（St.B[SE] -0.27[0.12]至-0.61[0.12]）。纵向分析显示，AD 痴呆患者的 SYT1 和 NPTX 水平随时间下降（St.B[SE] -0.10[0.04]至-0.15[0.05]），SCD/MCI-A+（St.B[SE] -0.07[0.03]至-0.12[0.03]），但 SCD/MCI-A- （pinteraction<0.05）组没有。AD 痴呆患者的 NfL 水平随时间升高与认知下降速度加快有关（St.B[SE] -1.75[0.58]），而其他组则没有（pinteraction<0.05）。
CSF 突触蛋白随时间表现出不同的斜率，表明复杂的突触动力学。较高的 SNAP-25 水平可能对预测 AD 早期阶段的认知下降有价值，而 NfL 随时间的增加与后期阶段的认知下降相关性更好。
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