ArticleAlzheimer's & dementia (New York, N. Y.)
Unraveling the impact of blood RANKL and OPG levels on Alzheimer's disease: Independent of bone mineral density and inflammation.
Article in Alzheimer's & dementia (New York, N. Y.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Osteoprotegerin and receptor activator of NF-kappaB ligand as biomarkers for bone resorption-related disorders.World journal of experimental medicine · 2026Review
- Alzheimer's Disease Risk Factor APOE4 Exerts Dimorphic Effects on Female Bone.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Unraveling the impact of blood RANKL and OPG levels on Alzheimer's disease: Independent of bone mineral density and inflammation.Alzheimer's & dementia (New York, N. Y.)Article
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5 authors.
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Abstract
introductionObservational studies have revealed a close relationship between reduced bone mineral density (BMD) and Alzheimer's disease (AD) risk. The receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) system, pivotal in regulating bone metabolism, has been implicated in brain function, but the causal impact on AD risk remains unclear.
methodsWe employed bi-directional Mendelian randomization (MR) and multivariable MR (MVMR) approaches to elucidate the effect of blood soluble RANKL (sRANKL) and OPG levels on AD, assessing whether this influence was independent of BMD and inflammation. Three distinct AD genome-wide association study (GWAS) data sets from the International Genomics of Alzheimer's Project (IGAP), UK Biobank (UKB), and FinnGen were utilized. Summary-level data on blood sRANKL and OPG were sourced from deCODE Genetics.
resultsGenetically predicted per standard deviation (SD) increase in blood sRANKL levels was significantly associated with a reduced risk of AD across all three AD GWAS data sets (IGAP: odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.72-0.94, DISCUSSION: Our study provides evidence that elevated sRANKL levels are causally linked to a reduced risk of AD, independent of BMD and inflammation. These findings enhance our understanding of the complex interactions between bone metabolism and AD. Highlights: Blood soluble receptor activator of nuclear factor kappa-B ligand (sRANKL) levels are linked to a reduced risk of Alzheimer's disease (AD).The association between sRANKL levels and AD is independent of bone mineral density (BMD) and inflammation.No causal link exists between blood osteoprotegerin levels and AD.AD does not affect blood levels of sRANKL or osteoprotegerin.
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