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Association of Vascular Endothelial Growth Factor Levels with Risk of Alzheimer’s Disease: A Systematic Review and Meta-Analysis

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Abstract

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative illness that leads to impairment of cognitive functions and memory loss. Even though there is a plethora of research reporting the abnormal regulation of VEGF expression in AD pathogenesis, whether the CSF and serum VEGF are increased in AD is an open question yet. In this study, the association of CSF and serum VEGF concentrations with the risk of Alzheimer’s disease was investigated using systematic review and meta-analysis.

Methods

A systematic literature search was carried out using online specialized biomedical databases of Web of Science, Pubmed, Scopus, Embase, and Google Scholar until Feb 2023 without restriction to the beginning time. The meta-analysis was performed using the random-effects model and only case-control publications describing VEGF concentrations in Alzheimer’s patients were considered for calculating the pooled effect size.

Results

In the systematic literature search, 6 and 13 studies met the inclusion criteria to evaluate CSF and serum VEGF concentrations of Alzheimer’s patients, respectively. This meta-analysis retrieved a total number of 2380 Alzheimer’s patients and 5368 healthy controls. Under the random-effects model in the meta-analysis, the pooled SMD for CSF and serum VEGF concentrations of Alzheimer’s patients were −0.13 (95%CI,−0.42–0.16) and 0.23 (95%CI,−0.27–0.73), respectively. Results of meta-regression analysis showed that the quality scores of papers and female sex ratios of participants did not affect the associations of VEGF concentrations with the risk of Alzheimer’s disease. However, the age average of patients significantly affects the associations of CSF VEGF concentrations with the risk of Alzheimer’s disease (P=0.051). There was a statistically significant subgroup effect for the disease severity of Alzheimer’s patients which modifies the associations of serum VEGF concentrations with the risk of Alzheimer’s disease (P<0.01) and subgroup analysis shows that study location modifies the associations of CSF and serum VEGF concentrations with the risk of Alzheimer’s disease (P<0.01).

Conclusion

The results show that the serum VEGF concentrations increased for Alzheimer’s patients in accordance with the increased expression of VEGF and the VEGF levels of Alzheimer’s patients decreased by increasing their disease severities. Therefore, in addition to detecting AD in the earliest stages of the disease, serum VEGF could be a promising biomarker to follow up on the disease and evaluate the clinical course of the disease.

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Acknowledgements

The authors would like to thank the research affair of Ilam University of Medical Sciences.

Funding

Funding: This study was funded by Ilam University of Medical Sciences.

Author information

Authors and Affiliations

  1. Department of Medical Physics, Faculty of Paramedical Sciences, Ilam University of Medical Sciences, Ilam, Iran

    Seyed Salman Zakariaee

  2. Non-Communicable Diseases Research Center, Ilam University of Medical Sciences, Ilam, Iran

    Seyed Salman Zakariaee

  3. Department of Midwifery, Faculty of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran

    N. Naderi

  4. Department of Immunology, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran

    E. Azizi

Authors
  1. Seyed Salman Zakariaee
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  2. N. Naderi
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  3. E. Azizi
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Contributions

Authors’ contributions: Seyed Salman Zakariaee: Content planning, Literature Search and Review, Data collection, Manuscript writing and editing, and Meta-Analysis. Negar Naderi: Literature Search and Review, Data collection, and Manuscript editing. Esfandyar Azizi: Project development, Literature Search and Review, Manuscript writing and editing.

Corresponding author

Correspondence to Seyed Salman Zakariaee.

Ethics declarations

Ethics approval and consent to participate: The study was approved by the local Medical Ethical Committee.

Competing interests: The authors declare that they have no competing interests.

Additional information

Consent for publication: Not applicable.

How to cite this article: S.S. Zakariaee, N. Naderi, E. Azizi, et al. Association of Vascular Endothelial Growth Factor Levels with Risk of Alzheimer’s Disease: A Systematic Review and Meta-Analysis. J Prev Alz Dis 2024; https://doi.org/10.14283/jpad.2024.18

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Zakariaee, S.S., Naderi, N. & Azizi, E. Association of Vascular Endothelial Growth Factor Levels with Risk of Alzheimer’s Disease: A Systematic Review and Meta-Analysis. J Prev Alzheimers Dis 11, 721–729 (2024). https://doi.org/10.14283/jpad.2024.18

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  • DOI: https://doi.org/10.14283/jpad.2024.18

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