Possible role for blood‐brain barrier disruption in patients with Alzheimer’s disease spectrum and non‐Alzheimer’s disease pathological changes

Abstract

AbstractBackgroundThe blood‐brain barrier (BBB) breakdown has been suggested as an early marker for Alzheimer’s disease (AD); yet the relationship between BBB breakdown and AD‐specific biomarkers based on the amyloid/tau/neurodegeneration (ATN) framework, is not clear. This study aimed to investigate the relationship between BBB permeability, AD‐specific biomarkers, and cognition in patients with cognitive decline.MethodIn this prospective observational study, we enrolled 62 participants with mild cognitive impairment or dementia between January 2019 and October 2020. All participants were assessed cognitive tests, amyloid PET, dynamic contrast enhanced MRI for BBB permeability (Ktrans), CSF studies for Aβ42/40 ratio, CSF phosphorylated tau Thr181 protein (p‐tau), CSF total tau protein (t‐tau), and structural MRI for neurodegeneration.ResultCompared with the Aβ‐G, the Aβ+G had a higher median Ktrans in the frontal cortices (P = 0.049). In Aβ‐G, Ktrans was positively correlated with CSF p‐tau level in the cerebral cortex (all p < 0.05 except for the occipital cortex). In Aβ+G, Ktrans of occipital cortices was related with CSF Aβ42/40 (rho = 0.403, p = 0.027), and CSF t‐tau level (rho = ‐0.404, p = 0.027), whereas, Ktrans of frontal (rho = ‐0.610, p<0.001), insular (r = ‐0.400, p = 0.028), parietal (rho = ‐0.446, p = 0.013) and temporal cortices (rho = ‐ 0.435, p = 0.016) was negatively related with hippocampal volume. When adjusting age and education, neither BBB permeability nor CSF biomarkers predict cognition.ConclusionOur results suggest that the relationship between BBB permeability and ATN biomarkers is evident, more interestingly, this relationship varies with the presence of Aβ plaque accumulation.