Genetic Insights Into the Role of Cathepsins in Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis: Evidence From Mendelian Randomization Study
2025

Genetic Insights Into Cathepsins and Neurodegenerative Diseases

Sample size: 111326 publication 10 minutes Evidence: moderate

Author Information

Author(s): Jiang Yanhong, Fan Wenhui, Li Yaxin, Xue Hua

Primary Institution: Department of Neurology Sichuan Taikang Hospital Chengdu Sichuan China

Hypothesis

Do genetically predicted levels of cathepsins have a causal effect on Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis?

Conclusion

Elevated cathepsin H levels increase the risk of Alzheimer's disease, while elevated cathepsin B levels decrease the risk of Parkinson's disease.

Supporting Evidence

  • Cathepsin H levels are linked to an increased risk of Alzheimer's disease.
  • Cathepsin B levels are associated with a decreased risk of Parkinson's disease.
  • No causal link was found between cathepsins and amyotrophic lateral sclerosis.

Takeaway

This study found that higher levels of a protein called cathepsin H can make you more likely to get Alzheimer's, while higher levels of cathepsin B can help protect against Parkinson's.

Methodology

A two-sample bidirectional Mendelian randomization study using publicly available GWAS data.

Potential Biases

Potential biases from the limited number of genetic variants used as instrumental variables.

Limitations

The study only included individuals of European ancestry, which may limit the generalizability of the findings.

Participant Demographics

Individuals of European ancestry.

Statistical Information

P-Value

0.005

Confidence Interval

1.011–1.069

Statistical Significance

p<0.001

Digital Object Identifier (DOI)

10.1002/brb3.70207

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