Dataset Information

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

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.

SUBMITTER: Zhang M

PROVIDER: S-EPMC10774172 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Zhang Miao M Qian Xiao-Hang XH Hu Jialin J Zhang Yaoyu Y Lin Xiaozhu X Hai Wangxi W Shi Kuangyu K Jiang Xufeng X Li Yao Y Tang Hui-Dong HD Li Biao B

European journal of nuclear medicine and molecular imaging 20231006 2

<h4>Purpose</h4>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.<h4>Methods</h4>We analyzed 85 patients with PET/MR imaging ...[more]

PMID: 37801139

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Project description:BackgroundThe aim of this longitudinal study was to assess with positron emission tomography (PET) the relationship between levels of inflammation and the loads of aggregated β-amyloid and tau at baseline and again after 2 years in prodromal Alzheimer's disease.MethodsForty-three subjects with mild cognitive impairment (MCI) had serial 11C-PK11195 PET over 2 years to measure inflammation changes, and 11C-PiB PET to determine β-amyloid fibril load; 22 also had serial 18F-Flortaucipir PET to determine tau tangle load. Cortical surface statistical mapping was used to localise areas showing significant changes in tracer binding over time and to interrogate correlations between tracer binding of the tracers at baseline and after 2 years.ResultsThose MCI subjects with high 11C-PiB uptake at baseline (classified as prodromal Alzheimer's disease) had raised inflammation levels which significantly declined across cortical regions over 2 years although their β-amyloid levels continued to rise. Those MCI cases who had low/normal 11C-PiB uptake at baseline but their levels then rose over 2 years were classified as prodromal AD with low Thal phase 1-2 amyloid deposition at baseline. They showed levels of cortical inflammation which correlated with their rising β-amyloid load. Those MCI cases with baseline low 11C-PiB uptake that remained stable were classified as non-AD, and they showed no correlated inflammation levels. Finally, MCI cases which showed both high 11C-PiB and 18F-Flortaucipir uptake at baseline (MCI due to AD) showed a further rise in their tau tangle load over 2 years with a correlated rise in levels of inflammation.ConclusionsOur baseline and 2-year imaging findings are compatible with a biphasic trajectory of inflammation in Alzheimer's disease: MCI cases with low baseline but subsequently rising β-amyloid load show correlated levels of microglial activation which then later decline when the β-amyloid load approaches AD levels. Later, as tau tangles form in β-amyloid positive MCI cases with prodromal AD, the rising tau load is associated with higher levels of inflammation.

Dataset Information

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

Purpose

Methods

Results

Conclusion

Publications

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

Similar Datasets

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