Blood-brain barrier breakdown is linked to tau pathology and neuronal injury in a differential manner according to amyloid deposition

Abstract

The 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 framework is not clear. This study investigated the relationship between BBB permeability, AD-specific biomarkers, and cognition in patients with cognitive impairment. In this prospective study, we enrolled 62 participants with mild cognitive impairment or dementia between January 2019 and October 2020. All participants were assessed through cognitive tests, amyloid positron emission tomography (PET), dynamic contrast-enhanced magnetic resonance imaging (MRI) for BBB permeability (Ktrans), cerebrospinal fluid studies for Aβ42/40 ratio, phosphorylated-tau Thr181 protein (p-tau), total tau protein (t-tau), and structural MRI for neurodegeneration. In amyloid PET (+) group, higher cortical Ktrans was associated with lower Aβ40 (r = −0.529 p = 0.003), higher Aβ42/40 ratio (r = 0.533, p = 0.003), lower p-tau (r = −0.452, p = 0.014) and lower hippocampal volume (r = −0.438, p = 0.017). In contrast, cortical Ktrans was positively related to t-tau level. (r = 0.489, p = 0.004) in amyloid PET (−) group. Our results suggest that BBB permeability is related to AD-specific biomarkers, but the relationship can vary by the presence of Aβ plaque accumulation.