ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2018
Amyloid β synaptotoxicity is Wnt-PCP dependent and blocked by fasudil.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 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 63 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 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
- A Novel Nogo-A Receptor Antagonist Peptide Impedes Alzheimer's Disease Pathology by Nogo-A/NgR/ROCK Signaling Pathway.CNS neuroscience & therapeutics · 2026Article
- Re-Purposing a Rho-Associated Coiled-Coil Kinase (ROCK) Inhibitor for Alzheimer's Disease.Journal of clinical medicine · 2026Article
- Amyloid Beta Oligomers as Early Triggers of Neuronal Cytoskeleton Dysfunction in Alzheimer's Disease.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Identifying synergistic combinations of repurposed treatments for Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2025Article
- DNA methylation-wide association study of prevalent and incident dementia in the US Health and Retirement Study.medRxiv : the preprint server for health sciences · 2025Article
- Leveraging Alzheimer's Disease Omics to Identify Pleiotropic Genes Contributing to Neurodegeneration in Primary Open-Angle Glaucoma.Molecular neurobiology · 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
- Oligomeric Amyloid-β and Tau Alter Cell Adhesion Properties and Induce Inflammatory Responses in Cerebral Endothelial Cells Through the RhoA/ROCK Pathway.Molecular neurobiology · 2024Article
- Danggui Shaoyao San Alleviates Early Cognitive Impairment in Alzheimer's Disease Mice Through IRS1/GSK3β/Wnt3a-β-Catenin Pathway.Brain and behavior · 2024Article
- Dickkopf-1 drives perineural invasion via PI3K-AKT signaling pathway in head and neck squamous cancer.MedComm · 2024Article
- Article
- Role of Rho-associated kinases and their inhibitor fasudil in neurodegenerative diseases.Frontiers in neuroscience · 2024Review
- The RhoA-ROCK1/ROCK2 Pathway Exacerbates Inflammatory Signaling in Immortalized and Primary Microglia.Cells · 2023Article
- The Multifaceted Role of WNT Signaling in Alzheimer's Disease Onset and Age-Related Progression.Cells · 2023Review
- Involvement of Paired Immunoglobulin-Like Receptor B in Cognitive Dysfunction Through Hippocampal-Dependent Synaptic Plasticity Impairments in Mice Subjected to Chronic Sleep Restriction.Molecular neurobiology · 2023Article
- Cerebrospinal fluid and serum proteomic profiles accurately distinguish neuroaxonal dystrophy from cervical vertebral compressive myelopathy in horses.Journal of veterinary internal medicine · 2023Article
- A genetic variant of the Wnt receptor LRP6 accelerates synapse degeneration during aging and in Alzheimer's disease.Science advances · 2023Article
3 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
22 authors at 13 institutions in 3 countries.
Funding
Abstract
introductionSynapse loss is the structural correlate of the cognitive decline indicative of dementia. In the brains of Alzheimer's disease sufferers, amyloid β (Aβ) peptides aggregate to form senile plaques but as soluble peptides are toxic to synapses. We previously demonstrated that Aβ induces Dickkopf-1 (Dkk1), which in turn activates the Wnt-planar cell polarity (Wnt-PCP) pathway to drive tau pathology and neuronal death.
methodsWe compared the effects of Aβ and of Dkk1 on synapse morphology and memory impairment while inhibiting or silencing key elements of the Wnt-PCP pathway.
resultsWe demonstrate that Aβ synaptotoxicity is also Dkk1 and Wnt-PCP dependent, mediated by the arm of Wnt-PCP regulating actin cytoskeletal dynamics via Daam1, RhoA and ROCK, and can be blocked by the drug fasudil. DISCUSSION: Our data add to the importance of aberrant Wnt signaling in Alzheimer's disease neuropathology and indicate that fasudil could be repurposed as a treatment for the disease.
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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.