ArticleTranslational psychiatry2018
A role for APP in Wnt signalling links synapse loss with β-amyloid production.
Article in Translational psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06362707 (A Placebo Controlled Randomized Double-blind Parallel Group 12-month Trial of Fasudil for the Treatment of Early Alzheimer's Disease), which is not on this map. Cited by 70 papers, 1 of them a synthesis 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.
A Placebo Controlled Randomized Double-blind Parallel Group 12-month Trial of Fasudil for the Treatment of Early Alzheimer's Disease (FEAD)
Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Neurodegenerative Disease Associated Pathways in the Brains of Triple Transgenic Alzheimer's Model Mice Are Reversed Following Two Weeks of Peripheral Administration of Fasudil.International journal of molecular sciences · 2023Pooled it
- Mapping cross-domain drivers of Alzheimer's disease risk through integrated network analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Re-Purposing a Rho-Associated Coiled-Coil Kinase (ROCK) Inhibitor for Alzheimer's Disease.Journal of clinical medicine · 2026Article
- Neuronal guidance signaling in neurodegenerative diseases: Key regulators that function at neuron-glia and neuroimmune interfaces.Neural regeneration research · 2026Article
- Modeling Alzheimer's disease with brain organoids: mechanisms, applications, and future directions.Frontiers in cell and developmental biology · 2026Review
- Cognitive decline and reduced bone mineral density under the bone-brain axis: mechanistic insights and imaging evaluation strategies.Frontiers in aging neuroscience · 2026Review
- Estimation of genetic parameters for hatching performance and genome-wide association analysis in Baicheng-You chickens.Frontiers in veterinary science · 2026Article
- The Impact of Air Pollution and Obesity on Cognitive Decline and Risk of Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Identifying synergistic combinations of repurposed treatments for Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2025Article
- UBE3A stabilization of β-catenin preserves synaptic proteins essential for motor and cognitive functions in Angelman Syndrome.Molecular autism · 2025Article
- Mapping cross-domain drivers of Alzheimer's disease risk through integrated network analysis.bioRxiv : the preprint server for biology · 2025Article
- Kinetic Model with Feedback Cycle for Age-Dependent Amyloid Beta Accumulation in Mice.International journal of molecular sciences · 2025Article
- Testosterone Delays Bone Microstructural Destruction via Osteoblast-Androgen Receptor-Mediated Upregulation of Tenascin-C.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Measurement characteristics and genome-wide correlates of lifetime brain atrophy estimated from a single MRI.Nature communications · 2025Article
- Unlocking Hope: Therapeutic Advances and Approaches in Modulating the Wnt Pathway for Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- Amyloid-β can activate JNK signalling via WNT5A-ROR2 to reduce synapse formation in Alzheimer's disease.Journal of cell science · 2025Article
- Wnt/β-catenin Signaling in Central Nervous System Regeneration.Advances in experimental medicine and biology · 2025Review
- Rock inhibitors in Alzheimer's disease.Frontiers in aging · 2025Review
- Exercise training exerts beneficial effects on Alzheimer's disease through multiple signaling pathways.Frontiers in aging neuroscience · 2025Review
- Comprehensive medicinal chemistry survey highlights a portfolio of lead molecules for Alzheimer's disease therapy.Frontiers in chemistry · 2025Review
10 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
13 authors at 7 institutions in 3 countries.
Funding
Abstract
In Alzheimer's disease (AD), the canonical Wnt inhibitor Dickkopf-1 (Dkk1) is induced by β-amyloid (Aβ) and shifts the balance from canonical towards non-canonical Wnt signalling. Canonical (Wnt-β-catenin) signalling promotes synapse stability, while non-canonical (Wnt-PCP) signalling favours synapse retraction; thus Aβ-driven synapse loss is mediated by Dkk1. Here we show that the Amyloid Precursor Protein (APP) co-activates both arms of Wnt signalling through physical interactions with Wnt co-receptors LRP6 and Vangl2, to bi-directionally modulate synapse stability. Furthermore, activation of non-canonical Wnt signalling enhances Aβ production, while activation of canonical signalling suppresses Aβ production. Together, these findings identify a pathogenic-positive feedback loop in which Aβ induces Dkk1 expression, thereby activating non-canonical Wnt signalling to promote synapse loss and drive further Aβ production. The Swedish familial AD variant of APP (APP
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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.