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

Abstract

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

Netrin-1: A Serum Marker Predicting Cognitive Impairment after Spinal Cord Injury

“…Glioblastoma is one of the most common tumors in neurosurgery, and evidence in recent years suggests that Netrin-1, as an atypical angiogenic ligand, may be involved in the promotion of neovascularization in glioblastoma [ 30 ]. Evidence that Netrin-1 is involved in the pathogenesis of Alzheimer's disease has been found in cells, animals, and clinical experiments, indicating that Netrin-1 may be involved in the regulation of neuroplasticity [ 31 – 33 ]. Studies on the regulation of Netrin-1 receptors in Parkinson's disease have also been reported [ 33 – 35 ].…”

“…Evidence that Netrin-1 is involved in the pathogenesis of Alzheimer's disease has been found in cells, animals, and clinical experiments, indicating that Netrin-1 may be involved in the regulation of neuroplasticity [ 31 – 33 ]. Studies on the regulation of Netrin-1 receptors in Parkinson's disease have also been reported [ 33 – 35 ]. Another study pointed out that serum Netrin-1 concentration decreased after brain injury and could be used as a biomarker of traumatic brain injury [ 36 ].…”

Bibliometric analysis of research on Alzheimer’s disease and non-coding RNAs: Opportunities and challenges

“…A recent review article also shows that ncRNAs in exosomes can mediate nerve inflammation and promote the development of AD ( Weng et al, 2022 ). In addition, memory deficits are the main characteristics of AD, and improving memory deficits by regulating ncRNAs is also a future research direction ( Ju et al, 2021 ; Xiao et al, 2021 ; Zhang G. J. et al, 2022 ).…”

Netrin-1 Stimulates Migration of Neogenin Expressing Aggressive Melanoma Cells

“…Our data suggest that Neogenin receptors could play an important role during the metastatic spread of melanoma towards Netrin-1-expressing tissues such as the brain. Interestingly, studies have shown that Alzheimer’s disease, a neurodegenerative process characterized by accumulation of amyloid beta in brain tissue, which results in functional/cognitive decline, is associated with poor Netrin-1 expression [ 42 , 43 , 44 ]. This is not surprising given the contribution of Netrin-1 to synaptic function, which is involved in learning and memory [ 33 , 45 ].…”