DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Alzheimer disease 3 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAlzheimer disease 3 maps to a 2-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for alzheimer disease 3 is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
presenilin 1 (PSEN1) — PSEN1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet pc1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8KCS · 2.4 Å · ligand 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE (PC1). Experimental structure, not a prediction.
What the evidence adds up to
Loss of the orphan receptor GPR3 reduced amyloid plaque burden in four different transgenic Alzheimer’s mouse models and improved memory in APP/PS1 mice, according to a 2015 study. The same study found that GPR3 expression was stable during aging in healthy human postmortem brain tissue, but two cohorts of Alzheimer’s postmortem tissue showed a correlation between elevated GPR3 and disease progression. A 2019 study identified rare variants in PLD3 that were associated with late-onset Alzheimer’s risk in European and Han Chinese cohorts; in a cellular model these variants reduced PLD3 activity and altered amyloid-β levels, possibly through an autophagy-dependent mTOR pathway. Both GPR3 and PLD3 are presented as potential therapeutic targets, but neither has been tested in humans for Alzheimer’s.
A 2012 review noted that existing Alzheimer’s treatments slow symptom progression for an average of only six months, do not work for all patients, and that only three therapies were in Phase III trials at that time, reflecting underinvestment. A 2013 editorial argued that drug repurposing is a promising avenue, pointing to existing drugs for hypertension, diabetes, and acne as candidates. A 2025 review confirmed that repurposed drugs have safety and dosing data from their original indications but lack intellectual property protection, which means they are rarely advanced to late-stage Alzheimer’s trials. Computational tools, omic studies, and electronic records can identify candidates, but the financial and structural barriers to running definitive trials remain.
A 2011 paper on biomarkers warned that it is often difficult to tell whether an Alzheimer’s treatment is effective, and proposed that biomarkers should meet criteria such as biological plausibility, statistical significance, dose dependence, convergence across measures, and replicability before they can replace clinical outcomes. Even then, the authors said biomarkers may only supplement, not supplant, clinical profiles. No biomarker has yet been validated as a surrogate endpoint for Alzheimer’s by regulators.
What is still missing is funding for late-stage trials of repurposed agents, a validated biomarker that can serve as a primary endpoint, and a reliable way to stratify patients who might respond to a given target. The mouse data for GPR3 and the cellular data for PLD3 have not been translated into human trials, and the few drugs that have reached Phase III have not produced durable cognitive benefits.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2008 · 525 citations · open access
Protective effects of NSAIDs on the development of Alzheimer disease
AbstractAbsorption, distribution, excretion and metabolism of methocarbamol in normal and pregnant dogs and in normal humans were investigated. In acute experiments on anesthetized dogs that received unlabeled or C<sup>14</sup>-metho-carbamol into a tied-off loop of the jejunum, C<sup>14</sup> and chromogenous compounds related to methocarbamol distributed themselves widely in the body and crossed the placenta into the fetus. The kidneys and liver were the main routes of excretion. When the drug was given in relatively large doses, the concentration of methocarbamol and methocarbamol metabolites in tissues was higher than expected on the basis of simple diffusion equilibrium between blood (tissue fluid) and cell water. After treatment with C<sup>14</sup>-methocarbamol, the specific activity of the lipoids of several organs was only about one-third that of the dry lipoid-free residue of the same organs. At best, 84% of the C<sup>14</sup> absorbed with the drug from the intestine could be recovered from urine, bile, blood and the main soft tissues. In short-term experiments, some dogs received daily doses of unlabeled methocarbamol orally for 2 weeks. Chromogenous materials equivalent to less than 1% of the total methocarbamol dose were found in the chief soft tissues 1 day to 3 weeks after the drug was discontinued. When a single dose of C<sup>14</sup>-methocarbamol was given to other dogs, 50 to 90% of the activity appeared in the urine, and 10 to 12% in the feces on the first day. Two human volunteers ingested methocarbamol for 3 consecutive days, during which quantitative urine collections were made. The urine was analyzed for chromogenous compounds before and after acid hydrolysis. When the results of the total 3-day urines were expressed as methocarbamol equivalents, less than 1% of the drug was detected before hydrolysis and about 10% after hydrolysis. Urinary excretion of chromogenous compounds ceased almost completely within 2 days after methocarbamol was discontinued. Several types of studies were undertaken on dogs to clarify the metabolic fate of C<sup>14</sup>-metho-carbamol. <i>In vivo</i> hydrolysis of the carbarnate ester was negligible. Radioautographs of paper chromatograms gave evidence of six fractions, one of which was unchanged methocarbamol. Methocarbamol and two metabolites appeared as glucuronides in dog urine. Some of the metabolites of methocarbamol were not chloroform extractable from hydrolyzed and alkalinized urine.
Science Translational Medicine · 2015 · 89 citations
Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer’s disease mouse models
AbstractThe orphan G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) GPR3 regulates activity of the γ-secretase complex in the absence of an effect on Notch proteolysis, providing a potential therapeutic target for Alzheimer's disease (AD). However, given the vast resources required to develop and evaluate any new therapy for AD and the multiple failures involved in translational research, demonstration of the pathophysiological relevance of research findings in multiple disease-relevant models is necessary before initiating costly drug development programs. We evaluated the physiological consequences of loss of Gpr3 in four AD transgenic mouse models, including two that contain the humanized murine Aβ sequence and express similar amyloid precursor protein (APP) levels as wild-type mice, thereby reducing potential artificial phenotypes. Our findings reveal that genetic deletion of Gpr3 reduced amyloid pathology in all of the AD mouse models and alleviated cognitive deficits in APP/PS1 mice. Additional three-dimensional visualization and analysis of the amyloid plaque burden provided accurate information on the amyloid load, distribution, and volume in the structurally intact adult mouse brain. Analysis of 10 different regions in healthy human postmortem brain tissue indicated that GPR3 expression was stable during aging. However, two cohorts of human AD postmortem brain tissue samples showed a correlation between elevated GPR3 and AD progression. Collectively, these studies provide evidence that GPR3 mediates the amyloidogenic proteolysis of APP in four AD transgenic mouse models as well as the physiological processing of APP in wild-type mice, suggesting that GPR3 may be a potential therapeutic target for AD drug development.
Expert Review of Neurotherapeutics · 2012 · 61 citations
New and emerging treatments for Alzheimer’s disease
AbstractAlzheimer's disease (AD) and other dementias represent a significant and increasing clinical challenge. This review highlights current treatment options for AD and the main focusses of therapies currently being evaluated in clinical trials and for future therapeutic development. Existing treatments slow the progression of symptoms of the disease, but their efficacy does not extend to all people with AD, and benefits are not conveyed beyond an average of 6 months. Despite the substantial economic cost and healthcare burden of AD, which is increasing as populations age, there are currently only three therapies being investigated in Phase III clinical trials. This emphasises the substantial caution and underinvestment in treatment development in this area and why it is critical to address the current lack of effective treatments to target the underlying pathology and disease process in Alzheimer's disease.
Nature Communications · 2025 · 49 citations · open access
Drug repurposing for Alzheimer’s disease and other neurodegenerative disorders
AbstractRepurposed drugs provide a rich source of potential therapies for Alzheimer’s disease (AD) and other neurodegenerative disorders (NDD). Repurposed drugs have information from non-clinical studies, phase 1 dosing, and safety and tolerability data collected with the original indication. Computational approaches, “omic” studies, drug databases, and electronic medical records help identify candidate therapies. Generic repurposed agents lack intellectual property protection and are rarely advanced to late-stage trials for AD/NDD. In this review we define repurposing, describe the advantages and challenges of repurposing, offer strategies for overcoming the obstacles, and describe the key contributions of repurposing to the drug development ecosystem. Repurposed drugs provide a rich source of potential therapies for Alzheimer’s disease (AD) and other neurodegenerative disorders (NDD). In this review, the authors discuss the advantages and challenges of repurposing, offer strategies for overcoming the obstacles and describe the key contributions of repurposing to drug development.
Frontiers in Neuroscience · 2019 · 15 citations · open access
PLD3 Rare Variants Identified in Late-Onset Alzheimer’s Disease Affect Amyloid-β Levels in Cellular Model
AbstractNext-generation sequencing studies have reported that rare variants in PLD3 were associated with increased risk of late-onset Alzheimer’s disease (LOAD) in European cohorts. The association has been replicated in a Han Chinese cohort, two rare variants p.I163M in exon7 and p.R356H in exon11 of PLD3 were found to be associated with LOAD risk. Whether these variants have deleterious effects on protein function, and the underlying mechanisms by which they influence LOAD pathogenesis are unknown. Our results are the first to validate the hypothesis that these variants could lead to reduced PLD3 activity and affect amyloid-β levels in cellular model of AD, possibly via autophagy-dependent mTOR signaling pathway, indicating that PLD3 may represent a new therapeutic target for AD.
International Journal of Alzheimer s Disease · 2011 · 12 citations · open access
Biomarkers to Measure Treatment Effects in Alzheimer′s Disease: What Should We Look for?
AbstractIt is often surprisingly difficult to tell whether a treatment for Alzheimer's disease is effective. Biomarkers might offer the potential of a quantifiable objective measure of treatment effectiveness. This paper suggests several criteria by which biomarkers might be evaluated as outcomes measures. These include biological plausibility, statistical significance, dose dependence, convergence across measures, and replicability. If biomarkers can meet these criteria, then, pending regulatory approval, they may have a role in the evaluation of treatment effectiveness in Alzheimer's disease. If not, their usefulness may be in supplementing, but not supplanting, clinical profiles of treatment effects.
Expert Opinion on Investigational Drugs · 2013 · 8 citations · open access
Is a potential Alzheimer's therapy already in use for other conditions? Can medications for hypertension, diabetes and acne help with the symptoms?
AbstractThere is an urgent need to develop and evaluate more effective pharmacological treatments for Alzheimer's disease (AD). This editorial explores the avenue of drug repositioning and outlines a number of existing treatments that show great promise as therapies, in addition to discussing the potential for high-throughput drug discovery techniques in this important field.
Relationship Between Neurodegenerative Diseases and Proton Pump Inhibitors Using Bioinformatics
AbstractProton pump inhibitors (PPIs) are a class of drugs used for the treatment of acid-related diseases by inhibiting gastric acid secretion. Although PPIs are considered safe and clinically beneficial in the short term, mounting evidence raises safety concerns about the long-term use of PPIs. Alzheimer’s disease (AD) is the most common form and cause of dementia and is one of the biggest public health challenges among neurodegenerative diseases in the elderly with no effective treatment to date. In recent years, there have been conflicting studies in patients receiving long-term PPIs regarding the risk of dementia and in particular AD. Some studies showed a strong positive relationship between PPIs and their impact on dementia and AD. We performed an in-depth review and analysis of existing studies and performed some docking to investigate the interaction between PPIs and dementia, AD-associated proteins, enzymes, and receptors. This study aims to provide possible new insights about the long-term safety of PPI employment and eventual cognitive impairment leading to dementia and later AD.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
