Interleukin-3 is associated with sTREM2 and mediates the correlation between amyloid-ß and tau pathology in Alzheimer's disease.
J Neuroinflammation
; 19(1): 316, 2022 Dec 29.
Article
in En
| MEDLINE
| ID: mdl-36578067
ABSTRACT
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 (Aß42, 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, Aß pathology (as measured by CSF Aß42) affected the development of tau pathology partly by modifying the levels of CSF IL-3 and CSF sTREM2. Furthermore, the effect of Aß 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 Aß pathology to tau pathology. It indicates that IL-3 may be a major factor in the spreading from Aß pathology to tau pathology to cognitive impairment.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Alzheimer Disease
/
Cognitive Dysfunction
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
J Neuroinflammation
Journal subject:
NEUROLOGIA
Year:
2022
Document type:
Article
Affiliation country:
China