Zhang, Miao; Qian, Xiao-Hang; Hu, Jialin; Zhang, Yaoyu; Lin, Xiaozhu; Hai, Wangxi; Shi, Kuangyu; Jiang, Xufeng; Li, Yao; Tang, Hui-Dong; Li, Biao (2024). Integrating TSPO PET imaging and transcriptomics to unveil the role of neuroinflammation and amyloid-β deposition in Alzheimer's disease. European journal of nuclear medicine and molecular imaging, 51(2), pp. 455-467. Springer 10.1007/s00259-023-06446-3
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PURPOSE
Despite the revealed role of immunological dysfunctions in the development and progression of Alzheimer's disease (AD) through animal and postmortem investigations, direct evidence regarding the impact of genetic factors on microglia response and amyloid-β (Aβ) deposition in AD individuals is lacking. This study aims to elucidate this mechanism by integrating transcriptomics and TSPO, Aβ PET imaging in clinical AD cohort.
METHODS
We analyzed 85 patients with PET/MR imaging for microglial activation (TSPO, [18F]DPA-714) and Aβ ([18F]AV-45) within the prospective Alzheimer's Disease Immunization and Microbiota Initiative Study Cohort (ADIMIC). Immune-related differentially expressed genes (IREDGs), identified based on AlzData, were screened and verified using blood samples from ADIMIC. Correlation and mediation analyses were applied to investigate the relationships between immune-related genes expression, TSPO and Aβ PET imaging.
RESULTS
TSPO uptake increased significantly both in aMCI (P < 0.05) and AD participants (P < 0.01) and showed a positive correlation with Aβ deposition (r = 0.42, P < 0.001). Decreased expression of TGFBR3, FABP3, CXCR4 and CD200 was observed in AD group. CD200 expression was significantly negatively associated with TSPO PET uptake (r =-0.33, P = 0.013). Mediation analysis indicated that CD200 acted as a significant mediator between TSPO uptake and Aβ deposition (total effect B = 1.92, P = 0.004) and MMSE score (total effect B =-54.01, P = 0.003).
CONCLUSION
By integrating transcriptomics and TSPO PET imaging in the same clinical AD cohort, this study revealed CD200 played an important role in regulating neuroinflammation, Aβ deposition and cognitive dysfunction.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine |
UniBE Contributor: |
Shi, Kuangyu |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1619-7089 |
Publisher: |
Springer |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
09 Oct 2023 13:01 |
Last Modified: |
09 Jan 2024 00:13 |
Publisher DOI: |
10.1007/s00259-023-06446-3 |
PubMed ID: |
37801139 |
Uncontrolled Keywords: |
Alzheimer’s disease Amyloid-β CD200 Neuroinflammation TSPO [18F]DPA-714 PET/MR |
BORIS DOI: |
10.48350/186963 |
URI: |
https://boris.unibe.ch/id/eprint/186963 |
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