Objective:

The involvement of Complement 1q(C1q) and Apolipoprotein E (ApoE) in the progression of Alzheimer's disease (AD) is complex due to the previously reported association between neuroinflammation and AD pathology. To investigate the role of C1q and ApoE interaction in neuroinflammation and AD pathology, we examined the correlation between cerebrospinal fluid (CSF) C1q, CSF ApoE, and CSF neuroinflammatory biomarkers and AD core biomarkers.

Background:

In recent years, increasing evidence suggests that the immune system plays a crucial role in the development of Alzheimer's disease, particularly the activation of the complement system, which may be closely associated with the pathological progression.  A previous study found that the interaction between ApoE and C1q might lead to increased inflammatory responses, thus promoting the development of AD. A recent Basic research found a link between the C1q-ApoE complexes and AD.

Design/Methods:

Here, we undertook an investigation of older adults CSF using two different proteomic platforms—SomaScan（n=579）and multiple reaction monitoring (MRM[n=207]). Linear regression analyses were conducted to explore the associations of CSF ApoE and C1q with CSF AD biomarkers. The mediation model and structural equation model (SEM) were conducted to explore the associations of ApoE and C1q with AD biomarkers.

Results:

Multiple linear regression showed that ApoE was positively associated with C1q in total participants and Alzheimer’s continuum participants. Mediation analyses indicated that C1q mediated the relationships between ApoE and AD biomarkers (mediation proportions range from 15.06 to 44.64%; p<0.05) except for amyloid-β and progranulin (PGRN). SEM yielded similar results, confirming these findings.

Conclusions:

Our findings provide evidence to suggest that C1q is linked to ApoE and mediates the correlation between AD core biomarkers and neuroinflammatory biomarkers, both of which indicate the complex link between C1q-ApoE and AD.