AUTHOR=Ju Ting , Sun Lina , Fan Yuwei , Wang Tianhang , Liu Yanchen , Liu Dan , Liu Tianyi , Zhao Chang , Wang Wenxin , Chi Lijun TITLE=Decreased Netrin-1 in Mild Cognitive Impairment and Alzheimer’s Disease Patients JOURNAL=Frontiers in Aging Neuroscience VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.762649 DOI=10.3389/fnagi.2021.762649 ISSN=1663-4365 ABSTRACT=Background and Objective

Inflammatory mediators are closely associated with the pathogenesis of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Netrin-1 is an axon guidance protein and despite its capacity to function as a neuroimmune guidance signal, its role in AD or MCI is poorly understood. In addition, the association among netrin-1, cognitive impairment and serum inflammatory cytokines such as interleukin-17 (IL-17) and tumor necrosis (TNF-α) remains unclear. The aim of this study was to determine serum levels of IL-17, TNF-α and netrin-1in a cohort of AD and MCI patients, and to study the relationship between these cytokines and cognitive status, as well as to assess the possible relationships between netrin-1 levels and inflammatory molecules.

Methods

Serum concentrations of netrin-1, TNF-α and IL-17 were determined in 20 AD patients, 22 MCI patients and 22 healthy controls using an enzyme-linked immunosorbent assay (ELISA). In addition, neuropsychological evaluations and psychometric assessments were performed in all subjects.

Results

Serum netrin-1 levels were decreased in AD and MCI patients and were positively correlated with Mini Mental State Examination (MMSE) scores. In contrast, serum TNF-α and IL-17 levels were elevated in AD and MCI cohorts and negatively correlated with MMSE scores. Serum netrin-1 levels were inversely related with TNF-α and IL-17 levels in AD, but not MCI, patients.

Conclusion

Based on the findings reported here, netrin-1 may serve as a marker for the early recognition of dementia and predict cognitive impairment.