Depression and Risk of Alzheimer's Disease: A Mendelian Randomization Study
Chongyang Liu1, Bao-Peng Liu2, Fang Pan1
1Department of Medical Psychology and Ethics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Current Alzheimer Research
|July 28, 2026
Summary
This study found no causal link between depression and Alzheimer's disease. Depression may be an early sign of Alzheimer's or share common causes, not directly cause it.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Depression frequently precedes Alzheimer's disease (AD) in older adults.
- The etiological relationship between depression and AD remains unclear.
Purpose of the Study:
- To investigate the potential causal relationship between depression and Alzheimer's disease using a robust genetic approach.
Main Methods:
- Genome-Wide Association Studies (GWAS) summary statistics for depression and AD were analyzed.
- Two-sample and three-sample Mendelian randomization analyses were employed.
- Large European cohorts, including UK Biobank data, were utilized.
Main Results:
- No significant association was found between genetically predicted broad depression and AD risk.
- Analyses for major depressive disorder yielded consistent results, showing no causal link.
- Sensitivity analyses indicated no significant bias from pleiotropy or genetic confounding.
Conclusions:
- The findings do not support a causal role for depression in the development of Alzheimer's disease.
- Depression may represent an early manifestation of AD pathology or share underlying mechanisms.
- Further research into shared pathological pathways is warranted.
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