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

  • Wei Tang
  • Yan Wang
  • Juan Cheng
  • Jie Yao
  • Yu-You Yao
  • Qiang Zhou
  • Shi-He GuanEmail author
Original Paper


The soluble amyloid protein procurer α (sAPPα) and β (sAPPβ) 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 sAPPα levels and 16 eligible studies with 1684 patients contributed to the analysis of CSF sAPPβ levels. CSF sAPPβ 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 sAPPα levels, there were no significant difference among groups. However, surprisingly, the resultant rankings graphically showed that pMCI populations have the highest levels of CSF sAPPα and sAPPβ. Furthermore, it seemed there was a positive correlation between CSF sAPPα and sAPPβ levels. The measurement of CSF sAPPα and sAPPβ levels may provide an alternative method for the diagnosis of early-stage AD, pMCI, which is conducive to preventive therapy.


Neurodegenerative diseases Alzheimer’s disease sAPPα sAPPβ Network meta-analysis 



Alzheimer’s disease


Corticobasal syndrome


Cerebrospinal fluid


Dementia with Lewy bodies


Frontotemporal dementia


Network meta-analysis


Parkinson’s disease dementia


Mild cognitive impairment progressed to AD dementia during the follow-up period


Progressive supranuclear palsy


Soluble amyloid protein procurer α


Soluble amyloid protein procurer β


Stable mild cognitive impairment


Vascular dementia



This work was funded in part by the Anhui Provincial Natural Science Foundation, Key Research and Development Plan “A” (Grant Numbers 1804h08020236); the Key Project of University Natural Science Foundation of Anhui Province (Grant Numbers KJ2018A0206).


The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Compliance with Ethical Standards

Conflict of interest

The authors have no conflict of interest to declare.

Ethical Approval

The manuscript is a retrospective report that does not require ethics committee approval at our institution.

Informed Consent

Written informed consent was obtained from all participants involved in this study.

Supplementary material

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Supplementary material 1 (XLS 43 kb)
12017_2019_8561_MOESM2_ESM.pdf (4.1 mb)
Supplementary material 2 (PDF 4188 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Wei Tang
    • 1
  • Yan Wang
    • 2
  • Juan Cheng
    • 1
  • Jie Yao
    • 1
  • Yu-You Yao
    • 3
  • Qiang Zhou
    • 1
  • Shi-He Guan
    • 1
    Email author
  1. 1.Department of Laboratory MedicineThe Second Hospital of Anhui Medical UniversityHefeiChina
  2. 2.Department of General SurgeryThe Second Hospital of Anhui Medical UniversityHefeiChina
  3. 3.Department of Clinical Laboratory Medicine, School of Public HealthAnhui Medical UniversityHefeiChina

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