SynthesisAnnals of neurology2020
Lipid lowering and Alzheimer disease risk: A mendelian randomization study.
Synthesis in Annals of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 4 syntheses or guidelines pooled it, 204 citations in OpenAlex.
- Summarizing attributable factors and evaluating risk of bias of Mendelian randomization studies for Alzheimer's dementia and cognitive status: a systematic review and meta-analysis.Systematic reviews · 2025Pooled it
- Genetically proxied therapeutic inhibition of lipid-lowering drug targets and risk of rheumatoid arthritis disease: a Mendelian randomization study.Clinical rheumatology · 2024Pooled it
- The landscape of the methodology in drug repurposing using human genomic data: a systematic review.Briefings in bioinformatics · 2024Pooled it
- Cholesteryl ester transfer protein (CETP) as a drug target for cardiovascular disease.Nature communications · 2021Pooled it
- Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease.Nature aging · 2021Trial
- PCSK9 inhibitors in neurodegenerative disorders: mechanisms, therapeutic potential, and clinical implications.Translational neurodegeneration · 2026Review
- Review
- Article
- A narrative review of PCSK9 inhibitors: from evolocumab to novel discoveries.Frontiers in pharmacology · 2026Review
- Exploration of the association of antidiabetic drugs with urolithiasis: A drug-targeted Mendelian randomization study.Asian journal of urology · 2026Article
- Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Alzheimer's Disease: Recent Advances and Controversies.Molecular neurobiology · 2025Review
- Twelve-year nationwide cohort study identifying risk factors for conversion from mild cognitive impairment to Alzheimer's disease.Scientific reports · 2025Article
- Exploring the effect of pre-clinical Alzheimer's disease on blood pressure using Mendelian randomisation and parental dementia as an instrumental variable in UK Biobank.BMC medicine · 2025Article
- Genetic insights into causal effects of lipids and lipid-modifying targets on calcific aortic valve stenosis: a Mendelian randomized study.Scientific reports · 2025Article
- Mendelian Randomization Assessment of the Genetic Effects of Lipid-Lowering Drugs on Digestive System Cancers.Food science & nutrition · 2025Article
- GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau.Nature communications · 2025Article
- Insights Into Causal Effects of Genetically Proxied Lipids and Lipid-Modifying Drug Targets on Cardiometabolic Diseases.Journal of the American Heart Association · 2025Article
- Unraveling the role of proteins in dementia: insights from two UK cohorts with causal evidence.Brain communications · 2025Article
- Exploring the Pleiotropy of PCSK9: A Wide Range of Influences from Lipid Regulation to Extrahepatic Function.Journal of inflammation research · 2025Review
- MosGraphFlow: a novel integrative graph AI model mining signaling targets from multi-omic data.BMC methods · 2025Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
objectiveTo examine whether genetic variation affecting the expression or function of lipid-lowering drug targets is associated with Alzheimer disease (AD) risk, to evaluate the potential impact of long-term exposure to corresponding therapeutics.
methodsWe conducted Mendelian randomization analyses using variants in genes that encode the protein targets of several approved lipid-lowering drug classes: HMGCR (encoding the target for statins), PCSK9 (encoding the target for PCSK9 inhibitors, eg, evolocumab and alirocumab), NPC1L1 (encoding the target for ezetimibe), and APOB (encoding the target of mipomersen). Variants were weighted by associations with low-density lipoprotein cholesterol (LDL-C) using data from lipid genetics consortia (n up to 295,826). We meta-analyzed Mendelian randomization estimates for regional variants weighted by LDL-C on AD risk from 2 large samples (total n = 24,718 cases, 56,685 controls).
resultsModels for HMGCR, APOB, and NPC1L1 did not suggest that the use of related lipid-lowering drug classes would affect AD risk. In contrast, genetically instrumented exposure to PCSK9 inhibitors was predicted to increase AD risk in both of the AD samples (combined odds ratio per standard deviation lower LDL-C inducible by the drug target = 1.45, 95% confidence interval = 1.23-1.69). This risk increase was opposite to, although more modest than, the degree of protection from coronary artery disease predicted by these same methods for PCSK9 inhibition.
interpretationWe did not identify genetic support for the repurposing of statins, ezetimibe, or mipomersen for AD prevention. Notwithstanding caveats to this genetic evidence, pharmacovigilance for AD risk among users of PCSK9 inhibitors may be warranted. ANN NEUROL 2020;87:30-39.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.