Blood-brain barrier integrity impacts the use of plasma amyloid-β as a proxy of brain amyloid-β pathology.

Abstract

Amyloid-β (Aβ) and tau can be quantified in blood. However, biological factors can influence the levels of brain-derived proteins in the blood. The blood-brain barrier (BBB) regulates protein transport between cerebrospinal fluid (CSF) and blood. BBB altered permeability might affect the relationship between brain and blood biomarkers. We assessed 224 participants in research (TRIAD, n=96) and clinical (BIODEGMAR, n=128) cohorts with plasma and CSF/positron emission tomography Aβ, p-tau, and albumin measures. Plasma Aβ42/40 better identified CSF Aβ42/40 and Aβ-PET positivity in individuals with high BBB permeability. An interaction between plasma Aβ42/40 and BBB permeability on CSF Aβ42/40 was observed. Voxel-wise models estimated that the association of positron emission tomography (PET), with plasma Aβ was most affected by BBB permeability in AD-related brain regions. BBB permeability did not significantly impact the relationship between brain and plasma p-tau levels. These findings suggest that BBB integrity may influence the performance of plasma Aβ, but not p-tau, biomarkers in research and clinical settings. BBB permeability affects the association between brain and plasma Aβ levels. BBB integrity does not affect the association between brain and plasma p-tau levels. Plasma Aβ was most affected by BBB permeability in AD-related brain regions. BBB permeability increases with age but not according to cognitive status.