A pilot cohort study of blood brain barrier permeability in Alzheimer’s disease using dynamic contrast enhanced magnetic resonance imaging

Blood–brain barrier (BBB) dysfunction is implicated as a key link between neuroinflammation and neurodegeneration in Alzheimer’s disease (AD). Peripheral inflammation may exacerbate cognitive decline by promoting BBB breakdown and impairing clearance of amyloid and tau, yet in vivo evidence for this hypothesis remains limited. We conducted a pilot cohort study to assess the feasibility of utilising dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to quantify BBB permeability in AD, and to explore associations with cognitive decline, peripheral inflammation, and neurodegeneration.

Fourteen participants with clinically diagnosed AD and 16 matched controls underwent baseline clinical, blood, urine, and DCE-MRI assessments. Thirteen AD participants were clinically reassessed after 12 months. BBB permeability was quantified using Patlak modelling in whole brain, grey and white matter, and selected regions of interest.

Serum cytokines, phosphorylated tau-181 (pTau-181), neurofilament light (NfL), and urinary neopterin were analysed. BBB permeability did not differ significantly between AD and controls across global or regional measures at baseline. However, higher baseline permeability in the left entorhinal cortex was significantly associated with greater cognitive decline over 12 months.

AD participants exhibited elevated serum interferon-γ relative to controls, and higher baseline interleukin-6 was associated with faster cognitive decline. This pilot study supports feasibility of regional DCE-MRI measurement in people with AD. Larger biomarker-confirmed cohorts are warranted to evaluate prognostic utility and to clarify the interaction between peripheral inflammation, BBB dysfunction and clinical progression in AD.

The authors express their sincere gratitude to all the patients and volunteers who participated in this study, without whom this research would not have been possible. This pilot project was supported by a pump-priming grant from the Alzheimer’s Research UK South Coast Network, a pump-priming grant from the University of Southampton Research Imaging Management Group, and Multiple Sclerosis Society grant number 996. Ian Galea and Jay Amin jointly supervised this work.

Clinical Neurosciences, School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK Beth Mary Stevens McCausland, Aravinthan Varatharaj, Nathan Thomas Matthew Huneke, Steevo Abraham, Rana Abadalkareem, Bartholomew Thomas, Claire Louise Gee, Amy Patricia Kunicki, Angela Darekar, Ian Galea & Jay Amin Memory Assessment and Research Centre, Hampshire and Isle of Wight Healthcare NHS Foundation Trust, Southampton, UK Beth Mary Stevens McCausland, Claire Louise Gee, Amy Patricia Kunicki & Jay Amin Wessex Neurological Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK Institute for Life Sciences, University of Southampton, Southampton, UK Department of Medical Physics, University Hospital Southampton NHS Foundation Trust, Southampton, UK School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK Interdisciplinary Dementia and Aging Centre (IdeAC), University of Southampton, Southampton, UK UK Dementia Research Institute, University College London Queen Square Institute of Neurology, London, UK Correspondence to Beth Mary Stevens McCausland. The authors declare no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.