MCP-1 levels in astrocyte-derived exosomes are changed in preclinical stage of Alzheimer's disease

Ting Wang; Yunxia Yao; Chao Han; Taoran Li; Wenying Du; Jinhua Xue; Ying Han; Yanning Cai

doi:10.3389/fneur.2023.1119298

MCP-1 levels in astrocyte-derived exosomes are changed in preclinical stage of Alzheimer's disease

Front Neurol. 2023 Mar 20:14:1119298. doi: 10.3389/fneur.2023.1119298. eCollection 2023.

Authors

Ting Wang^{1

2}, Yunxia Yao^{1

2}, Chao Han³, Taoran Li⁴, Wenying Du⁵, Jinhua Xue^{1

2}, Ying Han^{3

5

6}, Yanning Cai^{1

2

3

7}

Affiliations

¹ Department of Biobank, Xuanwu Hospital of Capital Medical University, Beijing, China.
² Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China.
³ National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital of Capital Medical University, Beijing, China.
⁴ Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Jangsu Province Hospital, Nanjing, China.
⁵ Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
⁶ Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Xuanwu Hospital of Capital Medical University, Beijing, China.
⁷ Beijing Geriatric Medical Research Center, Xuanwu Hospital of Capital Medical University, Beijing, China.

Abstract

Background: Alzheimer's disease (AD) is the most common form of dementia in older adults. There is accumulating evidence that inflammatory processes play a critical role in AD pathogenesis. In this study, we investigated whether inflammatory factors in plasma and astrocyte-derived exosomes (ADEs) from plasma are differentially expressed in the early stages of AD and their potential role in pathological processes in the AD continuum.

Method: We included 39 normal controls (NCs), 43 participants with subjective cognitive decline (SCD), and 43 participants with amnestic mild cognitive impairment (aMCI)/AD. IL-6, IL-8, and MCP-1 in plasma and ADEs from plasma were evaluated using a commercial multiplex Luminex-based kit.

Results: Pairwise comparisons between the groups showed no significant differences in plasma levels of IL-6, IL-8, or MCP-1. However, ADEs in the SCD group showed an increase in MCP-1 levels compared to the NC group. To differentiate the preclinical group, discriminant analysis was performed using sex, age, years of education, and genotype. This revealed a difference between the SCD and NC groups (area under the curve: 0.664). A Spearman correlation analysis of MCP-1 in plasma and ADEs showed no or weak correlation in the SCD (R = 0.150, p = 0.350) and aMCI/AD (R = 0.310, p = 0.041) groups, while a positive correlation in the NC group (R = 0.360, p = 0.026).

Conclusion: Plasma IL-6, IL-8, and MCP-1 levels were not significantly different. However, the concentration of MCP-1 in ADEs is slightly altered during the preclinical phase of AD, which could be a potential role of the central neuron system (CNS) immune response in the AD continuum.

Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT03370744.

Keywords: Alzheimer's disease; MCP-1; astrocyte-derived exosomes; immune; inflammation.

Associated data

ClinicalTrials.gov/NCT03370744

Grants and funding

This study was supported by the National Key R&D Program of China 2021YFC2501205 and the Science Innovation 2030—Brain Science and Brain-Inspired Intelligence Technology Major Project #2021ZD0201100 Task 1 #2021ZD0201101 and #2021ZD0201800 Task 1 #2021ZD0201801.