Are Blood-Based Protein Biomarkers for Alzheimer's Disease also Involved in Other Brain Disorders? A Systematic Review

Background: Alzheimer's disease (AD) biomarkers are urgently needed for both early and accurate diagnosis and prediction of disease progression. Past research has studied blood-based proteins as potential AD biomarkers, revealing many candidate proteins. To date only limited effort has been made to investigate the disease specificity of AD candidate proteins and whether these proteins are also involved in other neurodegenerative or psychiatric conditions. Objective: This review seeks to determine if blood-based AD candidate protein biomarkers are disease specific. Methods: Atwo-stage systematic literature search was conducted. Firstly, the most consistently identified AD protein biomarkers in blood were determined from a list of published discovery or panel-based (> 100 proteins) blood proteomics studies in AD. Secondly, an online database search was conducted using the 10 most consistently identified proteins to determine if they were involved in other brain disorders, namely frontotemporal lobe dementia, vascular dementia, Lewy body disease, Parkinson's disease, schizophrenia, depression, and autism. Results: Among the reviewed candidate proteins, plasma protease C1 inhibitor, pancreatic prohormone, and fibrinogen gamma chain were found to have the least evidence for non-specificity to AD. All other candidates were found to be affected by other brain disorders. Conclusion: Since we found evidence that the majority of AD candidate proteins might also be involved in other brain disorders, more research into the disease specificity of AD protein biomarkers is required.