Bilirubin/Albumin Levels in Patients with Alzheimer's Disease and Use of Intravenous Albumin for Its Treatment

Background: Bilirubin may be an upstream activator inducing Alzheimer's disease (AD). Methods: Bilirubin/albumin (ALB) levels in dementia patients with Aβ deposition were explored. Human albumin at a dose of 10 g every 2 weeks for 24 weeks was prescribed to AD patients to examine the effect of albumin on AD symptoms. Findings: Significantly higher indirect bilirubin (IBIL) levels and higher ratio of IBIL to albumin (IBIL/ALB) were reported in dementia patients with Aβ deposition, including AD, dementia with Lewy bodies and general paresis of insane.Intravenous albumin significantly lowered the ratio of IBIL to albumin (IBIL/ALB) at week 24. Analysis of the combined data of the entire 28 weeks of assessment period using the area under curve show significantly improvements in change of Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale scores and Clinical Dementia Rating Scale-Sum of Boxes scores. Interpretation: IBIL and IBIL/ALB was significantly higher in dementia patients with Aβ deposition. Bilirubin may be an upstream activator that induces AD. Consistent with these clinical findings, our intervention study shows that increasing serum bilirubin binding capacity from albumin by intravenous supplementation of human albumin yields benefit on daily function and dementia severity in AD patients. Targeting IBIL/ALB has highly potential for AD treatment. Trial Registration: The study was registered at chictr.org.cn (ChiCTR-IOR-17011539). Funding Statement: This work was supported by the National Funds for Developing Local Colleges and Universities (B16056001), Natural Science Foundation research team of Guangdong Province (2018B030312001) (to J.L), and Guangdong Natural Science Foundation (2017A030313662), Science and Technology Program of Guangzhou (201707010046) (to C.Z). Declaration of Interests: All authors declare that there are no conflicts of interest. Ethics Approval Statement: The Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital) approved this study. A written informed consent was obtained from the participants or their nearest relatives.