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

Abstract 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.