Department of Radiology, Brain Health Imaging Institute, Weill Cornell Medicine, 407 East 61 Street, 10065, New York, NY, USA.
Harvard Medical School, Boston, MA, USA.
Fluids Barriers CNS. 2024 Apr 2;21(1):30. doi: 10.1186/s12987-024-00530-y.
Reduced clearance of cerebrospinal fluid (CSF) has been suggested as a pathological feature of Alzheimer's disease (AD). With extensive documentation in non-human mammals and contradictory human neuroimaging data it remains unknown whether the nasal mucosa is a CSF drainage site in humans. Here, we used dynamic PET with [1-C]-Butanol, a highly permeable radiotracer with no appreciable brain binding, to test the hypothesis that tracer drainage from the nasal pathway reflects CSF drainage from brain. As a test of the hypothesis, we examined whether brain and nasal fluid drainage times were correlated and affected by brain amyloid.
24 cognitively normal subjects (≥ 65 years) were dynamically PET imaged for 60 min. using [1-C]-Butanol. Imaging with either [C]-PiB or [F]-FBB identified 8 amyloid PET positive (Aβ+) and 16 Aβ- subjects. MRI-determined regions of interest (ROI) included: the carotid artery, the lateral orbitofrontal (LOF) brain, the cribriform plate, and an All-turbinate region comprised of the superior, middle, and inferior turbinates. The bilateral temporalis muscle and jugular veins served as control regions. Regional time-activity were used to model tracer influx, egress, and AUC.
LOF and All-turbinate 60 min AUC were positively associated, thus suggesting a connection between the brain and the nose. Further, the Aβ+ subgroup demonstrated impaired tracer kinetics, marked by reduced tracer influx and slower egress.
The data show that tracer kinetics for brain and nasal turbinates are related to each other and both reflect the amyloid status of the brain. As such, these data add to evidence that the nasal pathway is a potential CSF drainage site in humans. These data warrant further investigation of brain and nasal contributions to protein clearance in neurodegenerative disease.
脑脊液（CSF）清除减少被认为是阿尔茨海默病（AD）的一种病理特征。尽管在非人类哺乳动物中有广泛的文献记载，并且人类神经影像学数据存在矛盾，但尚不清楚鼻腔粘膜是否是人类 CSF 的引流部位。在这里，我们使用动态 PET 结合 [1-C]-Butanol（一种具有高度通透性且无明显脑结合的示踪剂）来检验示踪剂从鼻腔途径排出反映 CSF 从脑排出的假说。作为该假说的检验，我们研究了脑和鼻腔液的排出时间是否相关，并受脑淀粉样蛋白的影响。
24 名认知正常的受试者（≥65 岁）进行了 60 分钟的 [1-C]-Butanol 动态 PET 成像。使用 [C]-PiB 或 [F]-FBB 进行成像，鉴定出 8 名淀粉样蛋白 PET 阳性（Aβ+）和 16 名 Aβ-受试者。MRI 确定的感兴趣区（ROI）包括：颈动脉、外侧眶额（LOF）脑、筛板和包含上、中、下鼻甲的全鼻甲区。双侧颞肌和颈静脉作为对照区。使用双侧 ROI 的时间-活性曲线来模拟示踪剂的流入、流出和 AUC。
LOF 和全鼻甲 60 分钟 AUC 呈正相关，因此提示大脑和鼻子之间存在联系。此外，Aβ+亚组表现出示踪剂动力学受损，表现为示踪剂流入减少和流出更慢。
数据表明，大脑和鼻甲的示踪剂动力学彼此相关，并且都反映了大脑的淀粉样蛋白状态。因此，这些数据增加了鼻腔途径是人类 CSF 潜在引流部位的证据。这些数据进一步证明了鼻腔和大脑在神经退行性疾病中对蛋白质清除的贡献。
