Neurodegeneration and Glial Activation Related CSF Biomarker as the Diagnosis of Alzheimer's Disease: A Systematic Review and an Updated Meta-analysis

Objective: Recently, neuron specific enolase (NSE), Visinin-like protein-1 (VLP-1), neurogranin (Ng), and YKL-40 have been identified as candidates for neuronal degeneration and glial activation biomarkers. Therefore, we perform a comprehensive meta-analysis to assess the diagnostic value of CSF NSE, VLP-1, Ng and YKL-40 in Alzheimer's disease (AD). Methods: We searched Pubmed, MEDLINE, EMBASE databases for research about the levels of CSF NSE, VLP-1, Ng and YKL-40 in AD patients compared with controls or other dementia diseases until Dec 2020. Results: The present meta-analysis contained a total of 51 studies comprising 6248 patients with dementia disorders and 3861 controls. Among them, there were 3262 patients with AD, 2456 patients with mild cognitive impairment (MCI), 173 patients with vascular dementia (VaD), 221 patients with frontotemporal dementia (FTD), and 136 with Lewy bodies dementia (DLB). Our study demonstrated that CSF NSE, VLP-1, Ng and YKL-40 levels were increased in AD as compared to healthy controls. We also observed that the CSF NSE level was higher in AD than VaD, suggesting CSF NSE might act as a key role in distinguishing between AD and VaD. Interestingly, there was a higher VLP-1 expression in AD, and a lower expression in DLB patients. Moreover, we found the CSF Ng level was increased in AD than MCI, implying CSF Ng might be a biomarker for identifying the progression of AD. Additionally, a significantly higher CSF YKL-40 level was detected not only in AD, but also in FTD, DLB, VaD, signifying YKL-40 was not sensitive in the diagnosis of AD. Conclusion: Our study confirmed that CSF levels of NSE, VLP-1, and Ng could be valuable biomarkers for identifying patients who are more susceptible to AD and distinguishing AD from other neurodegenerative dementia disorders.