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

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: These findings suggest that BBB integrity may influence the performance of plasma Aβ, but not p-tau, biomarkers in research and clinical settings.

Highlights: 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.