ArticleBrain and behavior2024
Causal relationship between PCSK9 inhibitor and common neurodegenerative diseases: A drug target Mendelian randomization study.
Article in Brain and behavior, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Cholesterol in amyotrophic lateral sclerosis: a bystander, a biomarker, or a target?Atherosclerosis plus · 2026Review
- PCSK9 inhibitors in neurodegenerative disorders: mechanisms, therapeutic potential, and clinical implications.Translational neurodegeneration · 2026Review
- Astrocytic HMGCR-Mediated Cholesterol Alleviated Parkinson's Disease Phenotypes by Inhibiting NF-κB Neuroinflammation.Molecular neurobiology · 2026Article
- Review
- The Use of Statins in Parkinson's and Alzheimer's Disease: A 2021-2025 State-of-the-Art Review of Clinical and Preclinical Evidence.Pharmacology research & perspectives · 2026Review
- The Roles of PCSK9 in Alzheimer's Disease: A Systematic Review of Clinical, Genetic, and Preclinical Evidence.Life (Basel, Switzerland) · 2025Review
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach.European journal of medical research · 2025Review
- Exploring the Pleiotropy of PCSK9: A Wide Range of Influences from Lipid Regulation to Extrahepatic Function.Journal of inflammation research · 2025Review
- Causal relationship between PCSK9 inhibitor and common neurodegenerative diseases: A drug target Mendelian randomization study.Brain and behavior · 2024Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
backgroundIn addition to lowering cholesterol levels, the proprotein convertase subtilis kexin 9 (PCSK9) inhibitor has a variety of effects, including anti-neuroapoptosis. However, the effects of PCSK9 inhibitors on neurodegenerative diseases are controversial. Therefore, we used drug-targeted Mendelian randomization (MR) analysis to investigate the effects of PCSK9 inhibitors on different neurodegenerative diseases.
methodsWe collected single nucleotide polymorphisms (SNPs) of PCSK9 from published statistics of genome-wide association studies and performed drug target MR analyses to detect a causal relationship between PCSK9 inhibitors and the risk of neurodegenerative diseases. We utilized the effects of 3-Hydroxy -3- methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitors (statin targets) for comparison with PCSK9 inhibitors. Coronary heart disease risk was used as a positive control, and primary outcomes included amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD).
resultsPCSK9 inhibitors marginally reduced the risk of ALS (OR [95%] = 0.89 [0.77 to 1.00], p = 0.048), while they increased the risk of PD (OR [95%] = 1.417 [1.178 to 1.657], p = 0.004). However, HMGCR inhibitors increased the risk of PD (OR [95%] = 1.907 [1.502 to 2.312], p = 0.001).
conclusionPCSK9 inhibitors significantly reduce the risk of ALS but increase the risk of PD. HMGCR inhibitors may be the risk factor for PD.
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