A vascular component to the selective vulnerability of the medial temporal lobe to tau pathology

The medial temporal lobe is widely recognized as an early site of pathological tau deposition, a central feature in the development of cognitive symptoms. As of now, the biological mechanisms underlying this selective vulnerability of the medial temporal lobe are not yet understood. Here, we tested whether alterations in medial temporal lobe arterial structure are associated with early tau accumulation and cognitive decline. We first applied a novel imaging methodology (super-selective arterial spin labelling) to map vascular supply to the medial temporal lobe. Next, we cross-sectionally investigated the relationship between medial temporal lobe artery diameters and tau burden, derived from magnetic resonance angiography and positron emission tomography imaging, in 151 cognitively unimpaired individuals (mean age: 67.6 years old). Finally, we examined whether artery diameter was correlated with the rate of cognitive decline in a separate cohort of 43 individuals (mean age: 74.2 years old). We found that the blood supply to the medial temporal lobe depended more on arteries from the anterior circulation than the posterior circulation. Individuals with small anterior choroidal artery diameters tended to show higher medial temporal lobe tau burden (r = -0.26, P = 0.001) and faster rates of cognitive decline (r = -0.40, P = 0.012). These results remained significant after adjusting for potential confounding factors such as amyloid burden. Our results show that anterior choroidal artery diameter may be an amyloid-independent determinant of tau pathology and cognitive decline. This suggests that the selective vulnerability of the medial temporal lobe may emerge from subpar perfusion from the anterior circulation.