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Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment
Published on: August 7, 2017
The interrelationships of CSF sTREM2, AD pathology, minimal depressive symptoms, and cognition in non-demented adults
Xue Liu1, Guang-Xiang Yu2, Mei Xue3
1Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
Background:
Microglial activation has been suggested to be involved in the pathogenesis of depression and Alzheimer's disease (AD). Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is a marker of microglial activation. The purpose of this study was to investigate the interrelationships of cerebrospinal fluid (CSF) sTREM2, AD pathology, as well as minimal depressive symptoms (MDSs), and cognition.
Methods:
A total of 545 non-demented individuals from the Alzheimer's Disease Neuroimaging Initiative cohort were included in our study. The average age of the total population was 72.6 years and the percentage of females was 42.6%. Linear regression models were conducted to investigate the linear relationships of MDSs with CSF sTREM2, AD pathology, cognition, and brain structure. Mediation models and structural equation models (SEM) were conducted to examine whether CSF sTREM2 mediated the relationships of MDSs with AD pathology and cognition.
Results:
Results revealed that individuals with MDSs had lower CSF sTREM2 levels than normal controls. Linear regression showed that MDSs were linearly associated with CSF sTREM2 (PFDR = 0.012) and amyloid biomarkers (PFDR < 0.05), as well as cognitive scores (PFDR < 0.05) and hippocampal volume (PFDR = 0.003). Mediation analyses revealed that CSF sTREM2 mediated the association between MDSs and amyloid pathology, with the mediating proportions ranging from 6.030 to 18.894%. However, SEM failed to reveal that MDS affected cognition through CSF amyloid pathology and CSF sTREM2.
Conclusions:
MDSs are associated with amyloid pathology and cognition. CSF sTREM2 may potentially be an intervenable target between depression and AD pathology.
Insights
Minimal depressive symptoms are linked to lower cerebrospinal fluid sTREM2 levels and altered Alzheimer's disease (AD) pathology. Soluble TREM2 may be a target for intervening in depression and AD.
Area of Science:
- Neuroscience
- Immunology
- Gerontology
Background:
- Microglial activation is implicated in the development of depression and Alzheimer's disease (AD).
- Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) serves as a biomarker for microglial activation.
Purpose of the Study:
- To investigate the relationship between cerebrospinal fluid (CSF) sTREM2 levels, AD pathology, minimal depressive symptoms (MDSs), and cognitive function.
- To explore the potential mediating role of CSF sTREM2 in the association between MDSs and AD pathology or cognition.
Main Methods:
- Analysis of 545 non-demented individuals from the Alzheimer's Disease Neuroimaging Initiative cohort.
- Linear regression models to assess relationships between MDSs, CSF sTREM2, AD biomarkers, cognition, and brain structure.
- Mediation and structural equation models (SEM) to examine the mediating effect of CSF sTREM2.
Main Results:
- Individuals with MDSs exhibited lower CSF sTREM2 levels compared to controls.
- MDSs were linearly associated with CSF sTREM2, amyloid biomarkers, cognitive scores, and hippocampal volume.
- CSF sTREM2 mediated the association between MDSs and amyloid pathology (6.030–18.894% mediation).
- SEM did not support MDS influencing cognition via CSF amyloid pathology and sTREM2.
Conclusions:
- Minimal depressive symptoms are associated with AD pathology and cognitive function.
- CSF sTREM2 presents a potential therapeutic target linking depression and AD pathology.
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