Measuring the Permeability of the Blood-Brain Barrier in Alzheimer's Disease Using Dynamic Contrast Enhanced MRI

AIMS: 1) To compare blood brain barrier (BBB) permeability between AD and controls. 2) To examine the relationship between BBB permeability and cognitive decline in AD. 3) To examine the relationship between BBB permeability and peripheral markers of inflammation. METHODS: This pilot study combines the use whole brain DCE-MRI, with measures of peripheral inflammation in serum and urine. This is a clinical cohort study with longitudinal and cross-sectional arms, involving n = 15 AD and n = 17 age and gender matched controls. BBB permeability is measured using DCE-MRI and inflammation is measured by comparing serum cytokine and urine neopterin concentrations. AD participants attend three study visits over 12 months; control participants attend two over one week. Urinary neopterin analysis is being conducted in February 2023.The 12 month follow up visits complete in May 2023. Both neopterin and longitudinal cognitive assessment data will be included in the poster presentation in July. RESULTS: AD and control groups were well matched with no significant differences in demographics and multi-morbidity. We measured blood cytokine profiles for IL-6, IL-8, IL-2, IL-4, IL-1b, IL-10, IL13, IL-12p70-, TNF-alpha and INF-gamma. Only INF-Gamma was significantly different; higher in AD vs Controls (mean ± SD; 28.758 ± 90.226 AD, 3.773 ± 2.256 Control, P = 0.03). There were no significant differences in markers of neurodegeneration NfL and pTau-181, or vascular markers VCAM1, ICAM1, CRP and SAA between the groups. Ki is being calculated for overall whole brain, white matter, grey matter and hippocampus regions; an interim analysis showed no significant differences between the tissue categories, but analysis is ongoing. CONCLUSION: There are currently no prognostic biomarkers that accurately predict decline in AD. We believe this pilot study will add to the literature about the utility and feasibility of DCE-MRI to measure BBB permeability. We hope that combining DCE-MRI with blood and urine biomarkers will further our knowledge of the pathophysiology of AD and help to develop minimally invasive biomarkers for identifying patients with AD, including those who are at risk of faster progression.