Association Analysis of Peripheral and CSF Biomarkers in Late Mild Cognitive Impairment.

Tao Zhang,Wei Kong,Shuaiqun Wang,Xiaoyang Mou

doi:10.3389/fgene.2020.00834

Tao Zhang, Wei Kong + Show 2 more

Open Access

https://doi.org/10.3389/fgene.2020.00834

Copy DOI

Abstract

Research shows that late mild cognitive impairment (LMCI) has a high risk of turning into Alzheimer’s disease (AD). Due to the invasion of detection methods and physical damage to the patients, it is not a convenient way to diagnose and detect early AD and LMCI by cerebrospinal fluid (CSF) data. So there is an urgent need to find the correlation between peripheral biological data and CSF data in the brain, and to find new diagnostic methods through changes in the peripheral biological data. Studies have shown that during the pathogenesis of LMCI and AD, peripheral immune cells specifically infiltrate into the brain through the blood–brain barrier, causing an imbalance in the brain’s immune response and dysregulating the clearance of Aβ in CSF. Therefore, in this paper, canonical correlation analysis (CCA) algorithm is presented to derive the correlation between peripheral and CSF biomarkers based on LMCI peripheral gene expression data and plasma marker information. Firstly, to explore the influence of the infiltration of peripheral blood immune cells on the brain, the abundance of 28 immune cells were calculated by using the gene set enrichment analysis algorithm of LMCI samples. Then, to identify the correlation between biomarkers inside and outside of the brain, we performed CCA to calculate the relationship between CSF and peripheral biomarkers. Results of CCA showed significant correlations between the variable sets of 8 peripheral biomarkers and the variable sets of CSF biomarkers (at 0.794). Finally, according to Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis, it was found that the obtained peripheral biomarkers are involved in many immune-related pathways and functions which can be activated in peripheral blood of LMCI patients. Most related genes enriched in immune-related pathways and functions were up-regulated. Through receiver operating characteristic curve (ROC) analysis, it was also found that FP40/FP42 and type 1 T helper can accurately predict the pathological changes of LMCI (at 0.747).

Highlights

Mild cognitive impairment (MCI) is a transitional stage in which normal aging develops into dementia (Stephan et al, 2007), but it is an unstable state
In this study, canonical correlation analysis (CCA) was introduced to explain the relationship between Cerebrospinal fluid (CSF) biomarkers and peripheral biomarkers
There is evidence that peripheral immune cells in Alzheimer’s disease (AD) recognize Aβ and treat it, present it to T cells, and trigger adaptive immunity (Józwik et al, 2012; Begum et al, 2014). This indicates that peripheral biomarkers may be potentially associated with AD

Summary

Introduction

Mild cognitive impairment (MCI) is a transitional stage in which normal aging develops into dementia (Stephan et al, 2007), but it is an unstable state. It can be seen that MCI is an early warning signal for the onset of AD Cerebrospinal fluid (CSF) marker analysis is an effective method for diagnosing MCI could be a differentiating marker for the detection of prodromal AD from clinically diagnosed MCI patients (Park et al, 2019). The study of MCI in Magaki et al (2007) found that the production of cytokines IL-6, IL-8, and IL-10 increased in peripheral blood, indicating that immune activation is an early phenomenon before AD. In this paper, the easyto-measure peripheral blood gene data and plasma biomarkers are used to establish an association with CSF markers in the brain of LMCI patients

Methods

Results

Conclusion