J Lipid Atheroscler.  2022 May;11(2):133-146. 10.12997/jla.2022.11.2.133.

Exploring the Genetic Associations Between the Use of Statins and Alzheimer's Disease

• Lee J
• Park S
• Kim Y
• Kim HM
• Oh CM

• KMID: 2531860
• DOI: http://doi.org/10.12997/jla.2022.11.2.133

Abstract

Objective
Alzheimer's disease (AD) is the most common cause of dementia. The statins have shown beneficial effects on cognitive functions and reduced the risk of dementia development. However, the exact mechanisms of statin effects in AD are not yet fully understood. In this study, we aimed to explore the underlying mechanisms of statin on AD.
Methods
We downloaded AD blood dataset (GSE63060) and statin-related blood gene expression dataset (GSE86216). Then we performed gene expression analysis of each dataset and compared blood gene expressions between AD patients and statin-treated patients. Then, we downloaded mouse embryonic neural stem cell dataset (GSE111945) and performed gene expression analysis.
Results
From the human blood dataset, we identified upregulated/downregulated genes in AD patients and statin-treated patients. Some of the upregulated genes (AEN, MBTPS1, ABCG1) in the blood of AD patients are downregulated in statin-treated patients. Several downregulated genes (FGL2, HMGCS1, PSME2, SRSF3, and ATG3) are upregulated in statintreated patients. Gene set enrichment analysis using mouse stem cell dataset revealed a significant relationship of Kyoto Encyclopedia of Genes and Genomes-defined pathway of AD in statin-treated neural stem cells compared to vehicle-treated neural stem cells (normalized enrichment score: −2.24 in male and −1.6 in female).
Conclusion
These gene expression analyses from human blood and mouse neural stem cell demonstrate the important clues on the molecular mechanisms of impacts of statin on AD disease. Further studies are needed to investigate the exact role of candidate genes and pathways suggested in our AD pathogenesis study.

Keyword

Alzheimer's disease; HMG-COA reductase inhibitor; Statin