Academic Journal
Interleukin-3 is associated with sTREM2 and mediates the correlation between amyloid-β and tau pathology in Alzheimer’s disease
| العنوان: | Interleukin-3 is associated with sTREM2 and mediates the correlation between amyloid-β and tau pathology in Alzheimer’s disease |
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| المؤلفون: | Wang, Zhi-Bo, Ma, Ya-Hui, Sun, Yan, Tan, Lan, Wang, Hui-Fu, Yu, Jin-Tai |
| المساهمون: | National Natural Science Foundation of China, Taishan Scholars Program of Shandong Province, Science and Technology Innovation 2030 Major Projects, Shanghai Municipal Science and Technology Major Project, Research Start-up Fund of Huashan Hospital, Excellence 2025 Talent Cultivation Program at Fudan University |
| المصدر: | Journal of Neuroinflammation ; volume 19, issue 1 ; ISSN 1742-2094 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2022 |
| الوصف: | Background Dysfunction of glial cell communication is involved in Alzheimer’s disease (AD) pathogenesis, and the recent study reported that astrocytic secreted interleukin-3 (IL-3) participated in astrocyte–microglia crosstalk and restricted AD pathology in mice, but the effect of IL-3 on the pathological progression of AD in human is still unclear. Methods A total of 311 participants with cerebrospinal fluid (CSF) IL-3, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and AD biomarkers were included from the Alzheimer’s disease Neuroimaging Initiative (ADNI). We assessed the associations of IL-3 with sTREM2 and AD biomarkers at baseline, and with cognitive change in longitudinal study. The mediation models were used to explore the potential mechanism of how IL-3 affects AD pathology. Results We found that CSF IL-3 was significantly associated with CSF sTREM2 and CSF AD core biomarkers (Aβ42, p-tau, and t-tau) at baseline, and was also markedly related to cognitive decline in longitudinal analysis. Moreover, mediation analysis revealed that CSF IL-3 modulated the level of CSF sTREM2 and contributed to tau pathology (as measured by CSF p-tau/t-tau) and subsequent cognitive decline. In addition, Aβ pathology (as measured by CSF Aβ42) affected the development of tau pathology partly by modifying the levels of CSF IL-3 and CSF sTREM2. Furthermore, the effect of Aβ pathology on cognitive decline was partially mediated by the pathway from CSF IL-3 and CSF sTREM2 to tau pathology. Conclusions Our findings provide evidence to suggest that IL-3 is linked to sTREM2 and mediates the correlation between Aβ pathology to tau pathology. It indicates that IL-3 may be a major factor in the spreading from Aβ pathology to tau pathology to cognitive impairment. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1186/s12974-022-02679-5 |
| DOI: | 10.1186/s12974-022-02679-5.pdf |
| DOI: | 10.1186/s12974-022-02679-5/fulltext.html |
| الاتاحة: | http://dx.doi.org/10.1186/s12974-022-02679-5 https://link.springer.com/content/pdf/10.1186/s12974-022-02679-5.pdf https://link.springer.com/article/10.1186/s12974-022-02679-5/fulltext.html |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.E882D678 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12974-022-02679-5 |
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