ArticleNeuron2014
Deficiency in LRP6-mediated Wnt signaling contributes to synaptic abnormalities and amyloid pathology in Alzheimer's disease.
Article in Neuron, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 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
139 citing papers in PubMed, 1 synthesis or guideline pooled it, 215 citations in OpenAlex.
- The involvement of the canonical Wnt-signaling receptor LRP5 and LRP6 gene variants with ADHD and sexual dimorphism: Association study and meta-analysis.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2019Pooled it
- Osteoporosis and Alzheimer's Disease: The Role of Sclerostin.Current osteoporosis reports · 2026Review
- Distinct single-nucleus RNA-seq changes among non-neuronal cells in ADNC, LATE-NC, and mixed pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Primary cilia-extracellular vesicle crosstalk in Alzheimer's disease: Emerging mechanisms and biomarker potential.Alzheimer's & dementia : the journal of the Alzheimer's Association · 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
- The Biological Basis, Mechanisms of Action, and Optimization Strategies of Exosomes Derived from Mesenchymal Stem Cells for the Treatment of Alzheimer's Disease.Molecular neurobiology · 2026Review
- Glycogen Synthase Kinase-3β Inhibition Ameliorates Synaptic and Mitochondrial Dysfunction in a Sporadic Alzheimer's Disease-Like Model.Molecular neurobiology · 2026Article
- Overexpression of WNT3a in the Hippocampus Can Partly Alleviate Deficits in Animal Models of Alzheimer's Disease.Neurochemical research · 2026Article
- Discovery of a CI-994 derivative as a dual modulator of class I HDACs and Wnt/β- catenin signaling for Alzheimer's disease therapy.bioRxiv : the preprint server for biology · 2026Article
- ISX9 activates the Wnt/β-catenin signaling pathway and exerts neuroprotective effects in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Genome-wide association study identifies novel variants in olfactory, vitamin A, vitamin B, and cadherin pathways associated with learning and memory.Scientific reports · 2025Article
- The Impact of Neurotoxin Proteins Trafficked by Primary Cilia and Extracellular Vesicles in Neurodegenerative Diseases.Biology · 2025Review
- UBE3A stabilization of β-catenin preserves synaptic proteins essential for motor and cognitive functions in Angelman Syndrome.Molecular autism · 2025Article
- Role of DENN Domain-Containing Protein 5b (dennd5b) during early embryonic development of zebrafish.Molecular biology reports · 2025Article
- Article
- Profilin and Non-Canonical Wnt Signaling: Coordinating Cytoskeletal Dynamics from Development to Disease.Journal of developmental biology · 2025Review
- miR-126-3p Protects Neonatal Rats With Hypoxic-Ischemic Brain Damage Through Targeting LPR6 via PKC/ERK Signaling Pathway.Physiological research · 2025Article
- Translational disease modeling of peripheral blood identifies type 2 diabetes biomarkers predictive of Alzheimer's disease.NPJ systems biology and applications · 2025Article
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Unlocking Hope: Therapeutic Advances and Approaches in Modulating the Wnt Pathway for Neurodegenerative Diseases.Molecular neurobiology · 2025Review
79 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
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Alzheimer's disease (AD) is an age-related neurological disorder characterized by synaptic loss and dementia. The low-density lipoprotein receptor-related protein 6 (LRP6) is an essential coreceptor for Wnt signaling, and its genetic variants have been linked to AD risk. Here we report that neuronal LRP6-mediated Wnt signaling is critical for synaptic function and cognition. Conditional deletion of Lrp6 gene in mouse forebrain neurons leads to age-dependent deficits in synaptic integrity and memory. Neuronal LRP6 deficiency in an amyloid mouse model also leads to exacerbated amyloid pathology due to increased APP processing to amyloid-β. In humans, LRP6 and Wnt signaling are significantly downregulated in AD brains, likely by a mechanism that depends on amyloid-β. Our results define a critical pathway in which decreased LRP6-mediated Wnt signaling, synaptic dysfunction, and elevated Aβ synergistically accelerate AD progression and suggest that restoring LRP6-mediated Wnt signaling can be explored as a viable strategy for AD therapy.
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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.