DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for tauopathy — 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 moduleTauopathy 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 tauopathy 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
apolipoprotein E (APOE) — APOE 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8AX9 · 1.549 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a 2015 pilot study, mice with tauopathy received monoclonal antibodies targeting pSer413‑tau or pSer396‑tau. The anti‑pSer413 antibody, injected intraperitoneally five times at 0.1 or 1 mg per shot into 10‑ to 14‑month‑old tau609 and tau784 mice, significantly improved memory in the Morris water maze. The anti‑pSer396 antibodies showed less effect. Cognitive improvement in the pSer413‑treated mice paralleled reductions in tau hyperphosphorylation, tau oligomer accumulation, synapse loss, tangle formation, and neuronal loss. The authors concluded that pSer413 is a promising target, but the study was a pilot in mice, with no human data.
A 2008 proteomic analysis compared temporal lobe tissue from four tauopathy cases and four aged controls. Twelve proteins were significantly upregulated in tauopathy brains, including glyceraldehyde 3‑phosphate dehydrogenase, uracil DNA glycosylase, human superoxide dismutase, isocitrate dehydrogenase subunit, synaptotagmin I, thioredoxin peroxidase 1, glial fibrillary acidic protein, P25 alpha, enoyl coenzyme A hydratase short chain 1, pyridoxine‑5'‑phosphate oxidase, Mn‑superoxide dismutase, and alpha enolase. Six proteins were expressed at lower levels: antioxidant protein 2, ferritin heavy chain, glutamate dehydrogenase precursor, peptidyl‑prolyl cis‑trans isomerase A, serum albumin precursor, and dihydropyrimidinase‑related protein 2. The study identified candidate proteins for understanding tauopathy mechanisms but did not test any intervention.
A 2025 study generated bigenic mice expressing both 3R and 4R tau isoforms. At 3, 6, and 9 months, these 3R/4Rtau‑tg mice showed increased total tau and phosphorylated tau in hippocampus and cortex compared to single‑isoform transgenic mice, along with greater astrogliosis and microglial activation. Bigenic mice had significantly worse spatial learning and memory and impaired nest building, interpreted as depression‑like or cognitive deficits. The authors argued that this model more completely recapitulates human tauopathy and should replace single‑isoform models for validating therapies. No drug was tested in this study.
What is still missing: no human trial of any antibody targeting pSer413‑tau has been reported; the proteomic findings remain correlative and unvalidated as therapeutic targets; the bigenic mouse model has not yet been used to test any candidate drug. Funding for clinical translation, a trial design that can measure cognitive endpoints in tauopathy patients, and patient stratification by tau isoform expression are all absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Clinical and Translational Neurology · 2015 · 80 citations · open access
Passive immunotherapy of tauopathy targeting pSer413‐tau: a pilot study in mice
AbstractOBJECTIVE: Cellular inclusions of hyperphosphorylated tau are a hallmark of tauopathies, which are neurodegenerative disorders that include Alzheimer's disease (AD). Active and passive immunization against hyperphosphorylated tau has been shown to attenuate phenotypes in model mice. We developed new monoclonal antibodies to hyperphosphorylated tau and sought high therapeutic efficacy for future clinical use. METHODS: Using more than 20 antibodies, we investigated which sites on tau are phosphorylated early and highly in the tauopathy mouse models tau609 and tau784. These mice display tau hyperphosphorylation, synapse loss, memory impairment at 6 months, and tangle formation and neuronal loss at 15 months. We generated mouse monoclonal antibodies to selected epitopes and examined their effects on memory and tau pathology in aged tau609 and tau784 mice by the Morris water maze and by histological and biochemical analyses. RESULTS: Immunohistochemical screening revealed that pSer413 is expressed early and highly. Monoclonal antibodies to pSer413 and to pSer396 (control) were generated. These antibodies specifically recognized pathological tau in AD brains but not normal tau in control brains according to Western blots. Representative anti-pSer413 and anti-pSer396 antibodies were injected intraperitoneally into 10-11- or 14-month-old mice once a week at 0.1 or 1 mg/shot 5 times. The anti-pSer413 antibody significantly improved memory, whereas the anti-pSer396 antibodies showed less effect. The cognitive improvement paralleled a reduction in the levels of tau hyperphosphorylation, tau oligomer accumulation, synapse loss, tangle formation, and neuronal loss. INTERPRETATION: These results indicate that pSer413 is a promising target in the treatment of tauopathy.
Identification of non-Alzheimer's disease tauopathies-related proteins by proteomic analysis
AbstractOBJECTIVES: To identify differentially expressed proteins between tauopathies cases and controls and to explore molecular mechanisms of tauopathies. METHOD: Two-dimensional gel electrophoresis (2DE) was applied to separate the total proteins of temporal lobe obtained at autopsy from four tauopathies cases and four aged subjects without clinical or pathologic involvement of nervous system. The silver or Coomassie brilliant blue stained gels were analysed by 2-DE software Image Master 2D Elite. Selected differential protein spots were identified with MALDI-TOF/TOF tandem mass spectrometry. RESULTS: Glyceraldehyde 3-phosphate dehydrogenase, uracil DNA glycosylase, human superoxide dismutase, isocitrate dehydrogenase subunit, synaptotagmin I, thioredoxin peroxidase 1, glial fibrillary acidic protein, P25 alpha, enoyl coenzyme A hydratase short chain 1, pyridoxine-5'-phosphate oxidase, Mn-superoxide dismutase and alpha enolase were significantly upregulated in tauopathies brains, whereas antioxidant protein 2, ferritin heavy chain, glutamate dehydrogenase precursor, peptidyl-prolyl cis-trans isomerase A, serum albumin precursor and dihydropyrimidinase-related protein 2 were lowly expressed in tauopathies brains. CONCLUSIONS: We identified a number of tauopathy-related proteins that might be useful for discovering the molecular mechanisms of tauopathies, which could also be helpful for diagnosing and treating these disorders.
Neurobiology of Disease · 2025 · 3 citations · open access
Differential roles of human tau isoforms in the modulation of inflammation and development of neuropathology
AbstractAlzheimer's disease (AD) is the most common tauopathy characterized by progressive accumulation of Aß and tau neuropathology. Tau is expressed in two major isoforms containing either 3 or 4C-terminal repeats, 3R and 4R. Despite tau isoforms occurring in roughly equimolar ratios in AD, the majority of research focus in developed mouse and in vitro models focus only on 4Rtau. To generate a more complete model of AD tauopathy and understand specific tau isoform-mediated neuropathology and neurodegeneration, we generated a transgenic mouse line expressing both 3Rtau and 4Rtau and determined how this impacted the timing and severity of neuropathological and behavioral changes. METHODS: 3Rtau-tg and 4Rtau-tg mice were crossed to generate 3R/4Rtau-tg bigenic mice. At 3, 6, and 9 months of age, mice were assessed for behavior, neuropathology and RNA expression. RESULTS: 3R/4Rtau bigenic mice expressed increased tau and phosphorylated tau in the hippocampus and cortex compared to single (3R or 4R) transgenic cohorts as early as 3-months of age and this was accompanied with increased astrogliosis and microglial activation. Bigenic mice had significantly greater behavioral deficits compared to either single transgenic littermates in spatial learning and memory as well as nest building, indicative of depression and/or cognitive deficits. CONCLUSION: This new mouse model of tauopathy more completely recapitulates the pattern, severity and accumulation of tau and associated neuropathology and behavioral changes observed in human tauopathies such as AD. 3R/4Rtau-tg bigenic mice should supplant existing single transgenic tau models for general validation of therapeutic targets and investigations of novel therapies on tauopathy endpoints.
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.
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