Department of Radiology, Weill Cornell Medicine, Cornell University, Brain Health Imaging Institute, 407 East 61 Street, New York, NY, 10021, USA.
Department of Radiology, New York University School of Medicine, New York, NY, USA.
Fluids Barriers CNS. 2022 Mar 14;19(1):21. doi: 10.1186/s12987-022-00318-y.
In sporadic Alzheimer's disease (AD), brain amyloid-beta (Aβ) deposition is believed to be a consequence of impaired Aβ clearance, but this relationship is not well established in living humans. CSF clearance, a major feature of brain glymphatic clearance (BGC), has been shown to be abnormal in AD murine models. MRI phase contrast and intrathecally delivered contrast studies have reported reduced CSF flow in AD. Using PET and tau tracer F-THK5117, we previously reported that the ventricular CSF clearance of the PET tracer was reduced in AD and associated with elevated brain Aβ levels.
In the present study, we use two PET tracers, F-THK5351 and C-PiB to estimate CSF clearance calculated from early dynamic PET frames in 9 normal controls and 15 AD participants.
we observed that the ventricular CSF clearance measures were correlated (r = 0.66, p < 0.01), with reductions in AD of 18 and 27%, respectively. We also replicated a significant relationship between ventricular CSF clearance (F-THK5351) and brain Aβ load (r = - 0.64, n = 24, p < 0.01). With a larger sample size, we extended our observations to show that reduced CSF clearance is associated with reductions in cortical thickness and cognitive performance.
Overall, the findings support the hypothesis that failed CSF clearance is a feature of AD that is related to Aβ deposition and to the pathology of AD. Longitudinal studies are needed to determine whether failed CSF clearance is a predictor of progressive amyloidosis or its consequence.
在散发性阿尔茨海默病（AD）中，脑内淀粉样蛋白-β（Aβ）沉积被认为是 Aβ清除受损的结果，但这一关系在活体人类中尚未得到很好的确立。脑内淋巴系统清除（BGC）的一个主要特征是 CSF 清除，在 AD 小鼠模型中已显示其异常。磁共振成像相位对比和鞘内给予对比剂的研究报告称 AD 患者 CSF 流动减少。我们之前使用 PET 和 tau 示踪剂 F-THK5117 报告称，AD 患者脑室 CSF 清除率降低，与脑内 Aβ水平升高有关。
在本研究中，我们使用两种 PET 示踪剂，F-THK5351 和 C-PiB，估计了 9 名正常对照者和 15 名 AD 参与者早期动态 PET 帧中的 CSF 清除率。
我们观察到脑室 CSF 清除率呈正相关（r=0.66，p<0.01），AD 患者的清除率分别降低了 18%和 27%。我们还复制了脑室 CSF 清除率（F-THK5351）与脑 Aβ负荷之间的显著关系（r=-0.64，n=24，p<0.01）。随着样本量的增加，我们的观察结果扩展到表明 CSF 清除率降低与皮质厚度和认知表现下降有关。
总的来说，这些发现支持了 CSF 清除失败是 AD 的一个特征的假设，与 Aβ沉积和 AD 的病理学有关。需要进行纵向研究以确定 CSF 清除失败是否是进行性淀粉样变性的预测因子还是其结果。
