James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, United States.
Parkinsonism Relat Disord. 2021 Nov;92:15-21. doi: 10.1016/j.parkreldis.2021.10.010. Epub 2021 Oct 13.
We sought to examine whether levels of soluble alpha-synuclein (α-syn), amyloid-beta (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau), as measured in cerebrospinal fluid (CSF), are associated with changes in brain volume in Parkinson's disease.
We assessed the 4-year change in total brain volume (n = 99) and baseline CSF α-syn, Aβ42, p-tau, and t-tau of Parkinson Progression Markers Initiative participants. We used linear mixed models to assess the longitudinal effect of baseline CSF biomarkers on total and regional brain volume and thickness as well as linear regression for cross-sectional analyses at baseline and year 2. All models were adjusted for age and gender; brain volume models also adjusted for baseline intracranial volume. Bonferroni correction was applied.
The 4-year change in total brain volume was -21.2 mm (95% confidence interval, -26.1, -16.3). There were no significant associations between the 4-year change in total brain volume and baseline levels of any CSF biomarker (all p-values > 0.05). On cross-sectional analyses, CSF Aβ42 was linearly associated with total brain volume at baseline (R = 0.60, p = 0.0004) and at year 2 (R = 0.66, p < 0.0001), with CSF Aβ42 < 1100 pg/ml, the threshold for brain amyloid pathology, associated with smaller total brain volume at baseline (p = 0.0010) and at year 2 (p = 0.0002). CSF α-syn was linearly associated with total brain volume at baseline (R = 0.58, p = 0.0044) but not at year 2 (R = 0.58, p = 0.1342).
Reduction in soluble Aβ42 is associated with lower total brain volume in Parkinson's disease.
我们旨在探讨测定于脑脊液（CSF）中的可溶性α-突触核蛋白（α-syn）、淀粉样β（Aβ42）、磷酸化 tau（p-tau）和总 tau（t-tau）水平是否与帕金森病的脑容量变化相关。
我们评估了帕金森病进展标志物倡议参与者的总脑容量（n=99）和基线 CSF α-syn、Aβ42、p-tau 和 t-tau 的 4 年变化。我们使用线性混合模型来评估基线 CSF 生物标志物对总脑和区域性脑容量和厚度的纵向影响，以及基线和第 2 年的横截面分析的线性回归。所有模型均进行了年龄和性别调整；脑容量模型还对基线颅内体积进行了调整。应用了 Bonferroni 校正。
总脑容量的 4 年变化为-21.2mm（95%置信区间，-26.1，-16.3）。总脑容量的 4 年变化与任何 CSF 生物标志物的基线水平均无显著相关性（所有 p 值>0.05）。在横截面分析中，CSF Aβ42 与基线时（R=0.60，p=0.0004）和第 2 年时（R=0.66，p<0.0001）的总脑容量呈线性相关，CSF Aβ42<1100pg/ml 是脑淀粉样蛋白病理的阈值，与基线时（p=0.0010）和第 2 年时（p=0.0002）的总脑容量较小相关。CSF α-syn 与基线时的总脑容量呈线性相关（R=0.58，p=0.0044），但与第 2 年时的总脑容量无关（R=0.58，p=0.1342）。
可溶性 Aβ42 的减少与帕金森病患者的总脑容量降低相关。
