Integrating TSPO PET imaging and transcriptomics to unveil the role of neuroinflammation and amyloid-β deposition in Alzheimer’s disease

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Abstract

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.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00259-023-06446-3.

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Most cited references 45

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A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease.

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Mild cognitive impairment as a diagnostic entity.

R C Petersen, George Perry (2005)

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Author and article information

Contributors

Xufeng Jiang: jxf10885@rjh.com.cn

Yao Li: yaoli@sjtu.edu.cn

Hui-dong Tang: thd10495@rjh.com.cn

Biao Li:

ORCID: http://orcid.org/0000-0002-0493-2062

lb10363@rjh.com.cn

Journal

Journal ID (nlm-ta): Eur J Nucl Med Mol Imaging

Journal ID (iso-abbrev): Eur J Nucl Med Mol Imaging

Title: European Journal of Nuclear Medicine and Molecular Imaging

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 1619-7070

ISSN (Electronic): 1619-7089

Publication date (Electronic): 6 October 2023

Publication date PMC-release: 6 October 2023

Publication date (Print): 2024

Volume: 51

Issue: 2

Pages: 455-467

Affiliations

[1 ]GRID grid.412277.5, ISNI 0000 0004 1760 6738, Department of Nuclear Medicine, , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, ; Shanghai, China

[2 ]GRID grid.412277.5, ISNI 0000 0004 1760 6738, Department of Geriatrics, , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, ; Shanghai, China

[3 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Medical Center On Aging of Ruijin Hospital, , Shanghai Jiao Tong University School of Medicine, ; Shanghai, China

[4 ]GRID grid.412277.5, ISNI 0000 0004 1760 6738, Department of Neurology and Institute of Neurology, , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, ; Shanghai, China

[5 ]School of Biomedical Engineering, Shanghai Jiao Tong University, ( https://ror.org/0220qvk04) Shanghai, China

[6 ]Department of Nuclear Medicine, Bern University Hospital, University of Bern, ( https://ror.org/02k7v4d05) Bern, Switzerland

[7 ]Department of Informatics, Technische Universität München, ( https://ror.org/02kkvpp62) Munich, Germany

Author information

Biao Li http://orcid.org/0000-0002-0493-2062

Article

Publisher ID: 6446

DOI: 10.1007/s00259-023-06446-3

PMC ID: 10774172

PubMed ID: 37801139

SO-VID: 1f53fd7c-8101-42bc-852d-28a11b01e08d

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 6 June 2023

Date accepted : 15 September 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 82372073

Award ID: 81971014

Award Recipient : Miao Zhang Hui-dong Tang

Funded by: FundRef http://dx.doi.org/10.13039/100017950, Shanghai Municipal Health Commission;

Award ID: 202240031

Award ID: shslczdzk03403

Award Recipient : Miao Zhang Biao Li

Funded by: Guangci Clinical Technology and Innovation Program(GCTIP) of Ruijin Hospital

Award ID: GCQH2023061

Award Recipient : Miao Zhang

Custom metadata

ScienceOpen disciplines: Radiology & Imaging

Keywords: tspo,[18f]dpa-714 pet/mr,cd200,neuroinflammation,amyloid-β,alzheimer’s disease

Data availability:

ScienceOpen disciplines: Radiology & Imaging

Keywords: tspo, [18f]dpa-714 pet/mr, cd200, neuroinflammation, amyloid-β, alzheimer’s disease

Integrating TSPO PET imaging and transcriptomics to unveil the role of neuroinflammation and amyloid-β deposition in Alzheimer’s disease

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Most cited references 45

The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease.

Mild cognitive impairment as a diagnostic entity.

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