ArticleMolecular psychiatry2015
HMGCR is a genetic modifier for risk, age of onset and MCI conversion to Alzheimer's disease in a three cohorts study.
Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer's disease.Alzheimer's research & therapy · 2017Pooled it
- Effect of simvastatin on CSF Alzheimer disease biomarkers in cognitively normal adults.Neurology · 2017Trial
- Sparse neuronal C4 elevation induces network-wide transcriptomic and lipid-droplet remodeling in the cortical microenvironment.PLoS computational biology · 2026Article
- Parent-of-origin effects in Alzheimer's liability dissociate neurocognitive and cardiovascular traits in at-risk individuals.Cell reports. Medicine · 2026Article
- Review
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Pharmacological modulation of the PI3K/AKT/GSK3β axis: a new frontier in Alzheimer's disease treatment.Inflammopharmacology · 2026Review
- Mechanisms, Mediators, and Pharmacological Approaches Targeting Brain Cholesterol Transport in Alzheimer's Disease.Current pharmaceutical design · 2026Review
- HMGCR genetic variability in Parkinson's disease in a Spanish cohort: associations with lipid metabolism and early onset.Journal of neurology · 2025Article
- Targeting of PP2 A/GSK3β/PTEN Axis in Alzheimer Disease: The Mooting Evidence, Divine, and Devil.Cellular and molecular neurobiology · 2025Review
- Genetic Polymorphisms in theInternational journal of molecular sciences · 2024Article
- Mechanisms of 3-Hydroxyl 3-Methylglutaryl CoA Reductase in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Investigation of the Relationship between Apolipoprotein E Alleles and Serum Lipids in Alzheimer's Disease: A Meta-Analysis.Brain sciences · 2023Review
- Brain structure and allelic associations in Alzheimer's disease.CNS neuroscience & therapeutics · 2023Article
- Statins Use in Alzheimer Disease: Bane or Boon from Frantic Search and Narrative Review.Brain sciences · 2022Review
- Exploring the Genetic Associations Between the Use of Statins and Alzheimer's Disease.Journal of lipid and atherosclerosis · 2022Article
- Drug repurposing using meta-analysis of gene expression in Alzheimer's disease.Frontiers in neuroscience · 2022Article
- Statins and cognition: Modifying factors and possible underlying mechanisms.Frontiers in aging neuroscience · 2022Review
- A Possible Role for HMG-CoA Reductase Inhibitors and Its Association withInternational journal of molecular sciences · 2021Review
- Abnormal brain cholesterol homeostasis in Alzheimer's disease-a targeted metabolomic and transcriptomic study.NPJ aging and mechanisms of disease · 2021Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Several retrospective epidemiological studies report that utilization of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibitors called statins at mid-life can reduce the risk of developing sporadic Alzheimer's disease (AD) by as much as 70%. Conversely, the administration of these inhibitors in clinically diagnosed subjects with AD confers little or no benefits over time. Here, we investigated the association between AD and HMGCR rs3846662, a polymorphism known to be involved in the regulation of HMGCR exon 13 skipping, in a founder population and in two distinct mixed North American populations of converting mild cognitively impaired (MCI) subjects (Alzheimer's disease Cooperative study (ADCS) and Alzheimer's disease Neuroimaging Initiative (ADNI) cohorts). Targeting more specifically women, the G allele negative (G-) AD subjects exhibit delayed age of onset of AD (P=0.017) and significantly reduced risk of AD (OR: 0.521; P=0.0028), matching the effect size reported by the apolipoprotein E type 2 variant. Stratification for APOE4 in a large sample of MCI patients from the ADCS cohort revealed a significant protective effect of G negative carriers on AD conversion 3 years after MCI diagnosis (odds ratio (OR): 0.554; P=0.041). Conversion rate among APOE4 carriers with the HMGCR's G negative allele was markedly reduced (from 76% to 27%) to levels similar to APOE4 non-carriers (27.14%), which strongly indicate protection. Conversion data from the independent ADNI cohort also showed significantly reduced MCI or AD conversion among APOE4 carriers with the protective A allele (P=0.005). In conclusion, HMGCR rs3846662 acts as a potent genetic modifier for AD risk, age of onset and conversion.
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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 OpenQuestion graph.