Decreased Netrin-1 in Mild Cognitive Impairment and Alzheimer's Disease Patients

• Published in: Frontiers in aging neuroscience Vol. 13; p. 762649
• Main Authors: Ju, Ting, Sun, Lina, Fan, Yuwei, Wang, Tianhang, Liu, Yanchen, Liu, Dan, Liu, Tianyi, Zhao, Chang, Wang, Wenxin, Chi, Lijun
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 16-02-2022; Frontiers Media S.A
• Subjects: Aging Neuroscience; Alzheimer's disease; Autoimmune diseases; Axon guidance; Chemokines; Cognition & reasoning; Cognitive ability; Consent; Cytokines; Dementia; Dementia disorders; Enzyme-linked immunosorbent assay; IL-17; Inflammation; Interleukin 17; Laboratories; Memory; mild cognitive impairment; Netrin-1; Neurodegenerative diseases; neuroinflammation; Neuropsychology; Pathogenesis; Serum levels; TNF-α; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; mild cognitive impairment; Alzheimer’s disease; TNF-α; neuroinflammation; netrin-1; IL-17
• ISSN: 1663-4365; 1663-4365
• DOI: 10.3389/fnagi.2021.762649

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