Related Experiment Video
Updated: May 28, 2025
Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment
Published on: August 7, 2017
Exploring the bidirectional relationships between alzheimer's disease and cerebral small vessel disease: Insights
Jihong Shang1, Tian Liu1, Wen Gong1
1Taian City Central Hospital, Taian 271000, PR China.
Insights
Cerebral small vessel disease (CSVD) significantly increases Alzheimer's disease (AD) risk, while certain inflammatory cytokines show varied effects. Targeting vascular health and inflammation may help manage neurodegenerative diseases like AD.
Area of Science:
- Neuroscience
- Genetics
- Epidemiology
Background:
- Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) are major neurological disorders with complex etiologies.
- Bidirectional causal links and the role of inflammatory cytokines in AD and CSVD pathogenesis remain incompletely understood.
Purpose of the Study:
- To investigate the potential bidirectional causal relationships between AD and CSVD.
- To examine the causal effects of 91 inflammatory cytokines on the risk of developing AD and CSVD using Mendelian randomization.
Main Methods:
- Utilized summary-level data from genome-wide association studies for AD, CSVD, and 91 inflammatory cytokines.
- Employed Mendelian randomization (MR) with inverse variance weighted (IVW) as the primary method, supplemented by MR-Egger and weighted median sensitivity analyses.
- Selected genetic variants strongly associated with each exposure as instrumental variables for robust causal inference.
Main Results:
- Genetically predicted CSVD was found to significantly increase the risk of AD (OR = 1.035, P = 0.001).
- No significant causal effect of AD on CSVD risk was observed (OR = 0.878, P = 0.257).
- Several inflammatory cytokines demonstrated significant associations: Axin1 and bNGF increased AD risk, CD5 and CXCL11 decreased AD risk, while FGF19 and TNFSF14 were protective against CSVD.
Conclusions:
- CSVD represents a significant risk factor for the development of AD.
- Specific inflammatory cytokines play differential roles, either increasing or decreasing the risk of AD and CSVD.
- Modulating vascular health and inflammatory pathways presents a potential therapeutic strategy for neurodegenerative diseases.
Objective:
This study aimed to elucidate the bidirectional causal relationships between Alzheimer's disease (AD), cerebral small vessel disease (CSVD), and the effect of inflammatory cytokines on AD and CSVD using Mendelian randomization (MR).
Method:
We employed publicly available summary-level data from genome-wide association studies for AD, CSVD, and 91 inflammatory cytokines. Genetic variants strongly associated with each risk factor were selected as instrumental variables. The inverse variance weighted (IVW) method was primarily used for causal inference, with sensitivity analyses including MR-Egger and weighted median estimators.
Results:
MR analysis revealed that genetically predicted CSVD significantly increased the risk of AD (odds ratio [OR] = 1.035, 95% CI, 1.015-1.056, P = 0.001). Conversely, AD did not significantly influence CSVD risk (OR = 0.878, 95% CI, 0.701-1.100, P = 0.257). Among inflammatory cytokines, Axin1 (OR = 1.082, 95% CI, 1.009-1.159, P = 0.026) and bNGF (OR = 1.061, 95% CI, 1.001-1.125, P = 0.048) increased AD risk, while CD5 (OR = 0.937, 95% CI, 0.887-0.991, P = 0.022) and CXCL11 (OR = 0.951, 95% CI, 0.912-0.992, P = 0.019) decreased AD risk. FGF19 (OR = 0.560, 95% CI, 0.405-0.773, P < 0.001) and TNFSF14 (OR = 0.744, 95% CI, 0.580-0.954, P = 0.020) were protective against CSVD.
Conclusion:
Our findings suggest that CSVD may increase AD risk, while specific inflammatory cytokines exhibit differential associations with these conditions. Targeting vascular health and inflammation may offer promising therapeutic avenues for managing neurodegenerative diseases.
More Related Videos
09:38Generalized Psychophysiological Interaction PPI Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
04:29Author Spotlight: Modeling Vascular Contributions to Alzheimer's Disease in Transgenic Mice
Published on: May 17, 2024
