Misery Perfusion and Tau Deposition in Atherosclerotic Major Cerebral Artery Disease: A 18 F-Florzolotau Positron Emission Tomography Study

Abstract

Background: 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. Methods: We prospectively evaluated the distribution of tau aggregate deposition using positron emission tomography and 18 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 18 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 15 O-gas positron emission tomography in the middle cerebral artery distributions. Results: 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. 18 F-florzolotau standardized uptake value ratio in this region was also greater than that in the contralateral hemisphere. In the ipsilateral hemisphere, 18 F-florzolotau standardized uptake value ratio positively correlated with OEF values. Conclusions: 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.