Department of Psychiatry, Graduate School of Medicine, Kyoto University, Japan (H.Y.).
Division of PET Imaging, Shiga Medical Centre Research Institute, Moriyama, Japan (S.K., K.K., M.I., C.O.).
Stroke. 2022 Dec;53(12):e500-e503. doi: 10.1161/STROKEAHA.122.040493. Epub 2022 Nov 7.
Studies using animal models have shown that cerebral hypoperfusion causes hyperphosphorylation of tau protein, leading to neuronal damage. However, the relationship between hypoperfusion and tau deposition in humans is unclear. Hence, we aimed to determine whether cerebral hypoperfusion leading to decreased blood flow relative to metabolic demand [increased oxygen extraction fraction (OEF), misery perfusion] is associated with increased tau deposition in patients with atherosclerotic internal carotid artery or middle cerebral artery disease.
We prospectively evaluated the distribution of tau aggregate deposition using positron emission tomography and F-florzolotau (PMPBB3 [1-fluoro-3-((2-((1E,3E)-4-(6-(methylamino)pyridine-3-yl)buta-1,3-dien-1-yl)benzo[d]thiazol-6-yl)oxy)propan-2-ol)]) in 8 patients with atherosclerotic disease of the internal carotid artery or middle cerebral artery. The standardized uptake value ratio of F-florzolotau at 100 to 110 minutes after injection was calculated using the cerebellar cortex as a reference region and was correlated with OEF obtained from O-gas positron emission tomography in the middle cerebral artery distributions.
Significant decreases in cerebral blood flow and cerebral metabolic rate of oxygen and increases in OEF were found in the hemisphere ipsilateral to the arterial lesion. F-florzolotau standardized uptake value ratio in this region was also greater than that in the contralateral hemisphere. In the ipsilateral hemisphere, F-florzolotau standardized uptake value ratio positively correlated with OEF values.
This pilot study with a small sample size suggests that increases in OEF-misery perfusion-may be associated with increased tau aggregates deposition in atherosclerotic internal carotid artery or middle cerebral artery disease.
动物模型研究表明，脑灌注不足会导致 tau 蛋白过度磷酸化，从而导致神经元损伤。然而，在人类中，灌注不足与 tau 沉积之间的关系尚不清楚。因此，我们旨在确定相对于代谢需求导致脑灌注不足（血流量增加、氧提取分数（OEF）增加、低灌注）是否与粥样硬化性颈内动脉或大脑中动脉疾病患者的 tau 沉积增加有关。
我们前瞻性地评估了 8 例颈内动脉或大脑中动脉粥样硬化患者使用正电子发射断层扫描和 F-florzolotau（PMPBB3 [1-氟-3-（（2-（（1E，3E）-4-（6-（甲氨基）吡啶-3-基）丁-1,3-二烯-1-基）苯并[d]噻唑-6-基）氧基）丙烷-2-醇]））的 tau 聚集沉积分布。使用小脑皮质作为参考区域，计算注射后 100 至 110 分钟时 F-florzolotau 的标准化摄取值比值，并与大脑中动脉分布区 O-气体正电子发射断层扫描获得的 OEF 相关。
在动脉病变同侧的半球中发现脑血流和脑氧代谢率显著降低，OEF 增加。该区域的 F-florzolotau 标准化摄取值比值也大于对侧半球。在同侧半球中，F-florzolotau 标准化摄取值比值与 OEF 值呈正相关。
这项小样本量的初步研究表明，OEF-低灌注-增加可能与粥样硬化性颈内动脉或大脑中动脉疾病中 tau 聚集沉积的增加有关。
