Non-invasive MRI of Blood-Cerebrospinal Fluid-Barrier Function: a Functional Biomarker of Early Alzheimer’s Disease Pathology

Abstract INTRODUCTION Choroid plexus (CP) dysfunction is thought to contribute to toxic protein build-up in neurodegenerative disorders, including Alzheimer’s disease (AD). However, the dynamics of this process remain unknown, mainly due to the paucity of in-vivo methods capable of assessing CP function. METHODS Here, we harness recent developments in Arterial Spin Labelling MRI to measure water delivery across the blood cerebrospinal fluid barrier (BCSFB) as a proxy for CP function, as well as cerebral blood flow (CBF), at different stages of AD progression in the widely used triple transgenic mouse model (3Tg), which recapitulates aspects of disease pathology. RESULTS Total BCSFB-mediated water delivery is significantly higher in 3Tg mice (>50%) from 8 weeks (preclinical stage), while tissue parameters such as CBF and T1 are not different between groups at all ages. DISCUSSION Our work shows changes in BCSFB function in the early stages of AD, providing a novel biomarker of pathology.