Cerebrospinal Fluid/Plasma Albumin Ratio as a Biomarker for Blood-Brain Barrier Impairment Across Neurodegenerative Dementias

Background: Previous studies have shown an association between disruption of the blood-brain-barrier (BBB) and dementias of different etiologies. The protein concentration of cerebrospinal fluid (CSF) 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 Q-Alb and CSF protein concentration in dementias of different etiologies and the possible confounding factors. Methods: A total of 510 patients and healthy controls were included in the current study. The patients were diagnosed with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), vascular dementia (VaD), or frontotemporal dementia (FTD). Results: We found that Q-Alb was significantly different between the groups (p=0.002, F=3.874). Patients with DLB and VaD showed the largest Q-Alb. Although not significant for CSF total protein, we found the same overall pattern for DLB and VaD. When examining confounding factors, we found a positive association with age and a lower Fazekas score in DLB as compared to VaD. Conclusion: These results suggest that Q-Alb can contribute to our understanding of the pathophysiological mechanisms in DLB, and Q-Alb may serve as a supplementary diagnostic marker. Furthermore, we found a positive association with age, which may be due to differences in vascular co-morbidities. In addition, in patients with DLB, the increased Q-Alb is not due to vascular lesions. Studies are needed to validate the possible diagnostic value of Q-Alb in a larger cohort.