ArticleNature metabolism2024
Osteocyte-derived sclerostin impairs cognitive function during ageing and Alzheimer's disease progression.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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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
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Population attributable fractions of a wide range of peripheral diseases for the burden of dementia.Nature human behaviour · 2026Pooled it
- Generalized osteoporosis but not axial osteopenia is associated with cognitive impairment in Parkinson's disease.Annals of medicine · 2026Article
- Biomaterials at the interface of bone-derived factors and inter-organ communication: Current evidence and future perspectives.Bioactive materials · 2026Review
- 7,8-Dihydroxyflavone ameliorates bone loss by regulating TRKB/AKT/FOXO3a pathway in a mouse model of alzheimer's disease.Psychopharmacology · 2026Article
- Sustainable Valorization of Biogenic Waste for Bone Repair and Regeneration: A Comprehensive Review of Eggshell and Aquatic Biomaterials.Journal of functional biomaterials · 2026Review
- The sixth sense of the brain: interoception in organoid study.Bone research · 2026Review
- The bone-cerebrovascular axis: effects of bone aging on neurovascular dysfunction and neurodegeneration.The Journal of clinical investigation · 2026Review
- Tunnelling Nanotube-Mediated Lysosome Sharing Promotes Osteocyte Survival via Transcellular Autophagy.Cell proliferation · 2026Article
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Regional heterogeneity in phenotypic and genetic associations between bone and brain in humans.Nature communications · 2026Article
- Alzheimer's Disease Risk Factor APOE4 Exerts Dimorphic Effects on Female Bone.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The neuro-skeletal crosstalk: Mechanisms, clinical implications, and smart material interventions.Journal of orthopaedic translation · 2026Review
- Osteocytes in the Metastatic Bone Niche: Mechanistic Pathways and Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Romosozumab versus teriparatide for risk of dementia in individuals with osteoporosis: a target trial emulation study.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Article
- Osteocyte Cell-Cell Communication Within and Beyond Bone.Current osteoporosis reports · 2026Review
- The puzzling duality of mesenchymal stem cells and adipocytes in bone marrow and ageing.npj aging · 2026Review
- Integrative clinical and genomic analyses reveal a causal role of GPNMB in the bone-brain axis of Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Exercise alleviates cognitive dysfunction in Alzheimer's disease mice via skeletal muscle-derived extracellular vesicles that enhance plaque clearance by microglia.Nature aging · 2026Article
- Lithium and the Brain-Bone Axis: A Bridge between Osteoporosis and Alzheimer's Disease.Current osteoporosis reports · 2026Review
- Sclerostin deficiency sensitizes white adipocytes to thermogenic signals that induce beiging in mice.Nature communications · 2026Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 1 country.
Funding
Abstract
Ageing increases susceptibility to neurodegenerative disorders, such as Alzheimer's disease (AD). Serum levels of sclerostin, an osteocyte-derived Wnt-β-catenin signalling antagonist, increase with age and inhibit osteoblastogenesis. As Wnt-β-catenin signalling acts as a protective mechanism for memory, we hypothesize that osteocyte-derived sclerostin can impact cognitive function under pathological conditions. Here we show that osteocyte-derived sclerostin can cross the blood-brain barrier of old mice, where it can dysregulate Wnt-β-catenin signalling. Gain-of-function and loss-of-function experiments show that abnormally elevated osteocyte-derived sclerostin impairs synaptic plasticity and memory in old mice of both sexes. Mechanistically, sclerostin increases amyloid β (Aβ) production through β-catenin-β-secretase 1 (BACE1) signalling, indicating a functional role for sclerostin in AD. Accordingly, high sclerostin levels in patients with AD of both sexes are associated with severe cognitive impairment, which is in line with the acceleration of Αβ production in an AD mouse model with bone-specific overexpression of sclerostin. Thus, we demonstrate osteocyte-derived sclerostin-mediated bone-brain crosstalk, which could serve as a target for developing therapeutic interventions against AD.
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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 Socratic graph.