Progression of Blood-Brain Barrier Leakage in Patients with Alzheimer's Disease as Measured with the Cerebrospinal Fluid/Plasma Albumin Ratio Over Time

Background: Studies have found a disruption of the blood-brain barrier (BBB) in patients with Alzheimer's disease (AD), but there is little evidence of the changes in the BBB over time. The cerebrospinal fluid's (CSF) protein concentration can be used as an indirect measurement for the permeability of the BBB using the CSF/plasma albumin quotient (Q-Alb) or total CSF protein. Objective: In the current study, we wanted to investigate the changes in Q-Alb in patients with AD over time. Methods: A total of 16 patients diagnosed with AD, who had at least two lumbar punctures performed, were included in the current study. Results: The difference in Q-Alb over time did not show a significant change. However, Q-Alb increased over time if the time interval was > 1 year between the measurements. No significant associations between Q-Alb and age, Mini-Mental State Examination, or AD biomarkers were found. Conclusion: The increase in Q-Alb suggests that there is an increased leakage through the BBB, which may become more prominent as the disease progresses. This may be a sign of progressive underlying vascular pathology, even in patients with AD without major vascular lesions. More studies are needed to further understand the role of BBB integrity in patients with AD over time and the association with the progression of the disease.