Decreased cerebrospinal fluid NDRG2 is associated with non-Alzheimer's disease derived mild cognitive impairment
Qing-ning Zhang, Wei Wu, Yong-ming Zhou, Lan-ke Yu, Xin-yuan Zhang, Jia-lin Wu, Si-yuan Song, Zhao-hui Yao,Background
Mild cognitive impairment (MCI) lacks clear clinical biomarkers. N-Myc downstream-regulated gene 2 (NDRG2) is predominantly localized in astrocytes and is implicated in cognitive function.
Objective
This study aims to explore whether cerebrospinal fluid (CSF) NDRG2 could predict MCI and investigate its underlying mechanisms of cognitive decline.
Methods
A total of 650 CSF samples were collected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, comprising 157 normal individuals, 366 MCI patients, and 127 Alzheimer's disease (AD) patients. One-way analysis of covariance (ANCOVA) was employed to assess differences in CSF NDRG2 levels among groups. Linear regression was used to analyze the correlation between NDRG2 and amyloid-β (Aβ), phosphorylated tau (p-tau), 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET), albumin quotient (Qalb), and growth-associated protein 43 (GAP43). Receiver operating characteristic (ROC) curves were used to examine the diagnostic performance of NDRG2 for MCI.
Results
CSF NDRG2 levels were significantly reduced in MCI, most prominently in non-Aβ and non-tau subgroups. NDRG2 discriminated Aβ-negative MCI with an area under the curve (AUC) of 0.719, but showed limited discriminatory capacity in Aβ+, tau+, and apolipoprotein E ε4 (
Conclusions
The present study demonstrates that NDRG2 is a potential biomarker for non-AD derived MCI and suggests its involvement in synaptic plasticity impairment.