CSF sAPPα and sAPPβ levels in Alzheimer's Disease and Multiple Other Neurodegenerative Diseases: A Network Meta-Analysis

The soluble amyloid protein procurer alpha (sAPP alpha) and beta (sAPP beta) have been postulated as promising new cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) and multiple other neurodegenerative diseases, but have failed to meet expectations with their often discordant and even contradictory findings to date. The aim of the study was to systematically explore this issue. Cochrane Library, PubMed, and CNKI were systematically searched without language or date restrictions. This network meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and also adhered to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Twenty studies, comprising ten groups, were eligible and included. Overall, 19 eligible studies with 1634 patients contributed to the analysis of CSF sAPP alpha levels and 16 eligible studies with 1684 patients contributed to the analysis of CSF sAPP beta levels. CSF sAPP beta levels are significantly higher in AD than in corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP); higher in Control than in Depression, CBS and PSP; higher in Parkinson's disease dementia (PDD) than in CBS and PSP; higher in mild cognitive impairment progressed to AD dementia during the follow-up period (pMCI) than in Depression and PSP; higher in stable mild cognitive impairment (sMCI) than in Depression. With regard to CSF sAPP alpha levels, there were no significant difference among groups. However, surprisingly, the resultant rankings graphically showed that pMCI populations have the highest levels of CSF sAPP alpha and sAPP beta. Furthermore, it seemed there was a positive correlation between CSF sAPP alpha and sAPP beta levels. The measurement of CSF sAPP alpha and sAPP beta levels may provide an alternative method for the diagnosis of early-stage AD, pMCI, which is conducive to preventive therapy.