DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Alzheimer disease type 1 — screening already-approved drugs against its 6-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 type 1 maps to a 6-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 type 1 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
myeloperoxidase (MPO) — MPO 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 hemdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5MFA · 1.2 Å · ligand PROTOPORPHYRIN IX CONTAINING FE (HEM). Experimental structure, not a prediction.
What the evidence adds up to
A 2012 autopsy study of 762 brain samples found that the MAPT H1 haplotype was associated with lower counts of neurofibrillary tangles in the middle frontal cortex (p<0.001) and inferior parietal cortex (p=0.005), and with lower senile plaque counts in the motor cortex (p=0.001). The same haplotype showed a nominal association with increased Lewy body counts in two cortical regions, but this did not survive correction for multiple testing. The APOE ε4 allele was strongly associated with overall Alzheimer-type pathology (all p≤0.001). No association with Alzheimer or Lewy body pathology was found for the SNCA rs356165 variant or the MAPT H1-specific SNP rs242557.
A 2020 study used zebrafish with a mutation orthologous to a human early-onset familial Alzheimer’s disease (EOfAD) mutation in SORL1, alongside a complete loss-of-function mutation. Brain transcriptome analysis of young adult fish revealed subtle effects on genes involved in energy production, mRNA translation and mTORC1 signalling in both the EOfAD-like and null heterozygotes, suggesting these effects arise from sorl1 haploinsufficiency. The EOfAD-mutation carriers also showed changes not seen in the null heterozygotes, suggesting a gain-of-function effect. Fish lacking wild-type sorl1 altogether (transheterozygotes) showed distinct transcriptome changes including effects on iron homeostasis. A 2025 report identified a novel likely pathogenic SORL1 mutation in a pedigree with five members affected by early-onset Alzheimer’s disease, noting that the contribution of SORL1 mutations to heritability is not well established and that reporting new familial mutations is important.
Two review articles from 2013 and 2022 discuss drug repurposing for Alzheimer’s disease. The 2013 editorial mentions existing treatments for hypertension, diabetes and acne as showing promise, but provides no data. The 2022 chapter lists fasudil, phenserine, antiviral drugs and GLP-1 analogs as high-priority repurposing candidates, but gives no trial results or effect sizes. No clinical efficacy data from repurposed drugs in Alzheimer’s patients are presented in any of these abstracts.
What is still missing: adequately powered randomised controlled trials of any repurposed candidate in Alzheimer’s disease, with clear endpoints and long follow-up. The genetic findings remain associative or based on small pedigrees and animal models, without proven therapeutic targets. Patient stratification by genotype (e.g. MAPT H1, SORL1 mutation status) has not been tested in a clinical trial. Funding for such trials, and for the necessary biomarker and imaging work, is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Neurology Neurosurgery & Psychiatry · 2012 · 52 citations · open access
An evaluation of the impact of<i>MAPT</i>,<i>SNCA</i>and<i>APOE</i>on the burden of Alzheimer's and Lewy body pathology
AbstractPURPOSE: The study investigates the effects of genetic factors on the pathology of Alzheimer's disease (AD) and Lewy body (LB) diseases, including Parkinson's disease and dementia with Lewy bodies. METHODS: A multicentre autopsy series (762 brain samples) with AD, LB or vascular pathology was examined. The effects of the tau gene (MAPT) H1 haplotype, the H1 specific SNP rs242557, APOE and the α-synuclein gene (SNCA) 3'UTR SNP rs356165 on the burden of AD and LB pathology were assessed. Neurofibrillary tangles (NFTs) were counted in four brain regions, senile plaques in five and LBs in four. Braak NFT stage, brain weight and presence of vascular pathology were also documented. RESULTS: MAPT H1 associated with lower counts of NFTs in the middle frontal (p<0.001) and inferior parietal (p=0.005) cortices, and also with lower counts of senile plaques in the motor cortex (p=0.001). Associations of MAPT H1 with increased LB counts in the middle frontal cortex (p=0.011) and inferior parietal cortex (p=0.033) were observed but were not significant after multiple testing adjustment. The APOE ε4 allele was strongly associated with overall Alzheimer type pathology (all p≤0.001). SNCA rs356165 and the MAPT H1 specific SNP rs242557 did not associate with AD or LB pathology. CONCLUSION: This study shows for the first time that MAPT H1 is associated with reduced Alzheimer type pathology which could have important implications for the understanding of disease mechanisms and their genetic determinants.
Sundowning Syndrome: A Possible Marker of Frailty in Alzheimer’s Disease?
AbstractThe term "sundowning" describes a clinical phenomenon characterized by late afternoon exacerbation of behavioural symptoms in dementia. Beyond this clinical definition, the debate around this concept is not properly solved, because many authors define it in different ways, mentioning various hypothetical etiological explanations. It represents a concrete problem, which is difficult to manage for physicians and caregivers, and is probably linked to various biological, psychological and social aspects. As recently reported, the sundowning phenomenon is a predictor of faster cognitive decline in Alzheimer's disease, and as such can represent a possible marker of frailty in this illness. This article presents an overview of the biological understanding and possible pharmacological and non-pharmacological treatment of this condition.
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.
Journal of Alzheimer s Disease Reports · 2025 · 3 citations · open access
A novel <i>SORL1</i> mutation in a pedigree affected by early-onset Alzheimer's disease
AbstractFamilial cases of Alzheimer's disease (AD) with autosomal dominant transmission and early onset have a prevalence around 1%. Since only a small fraction of them has a monogenic inheritance due to APP, PSEN1 , and PSEN2 genes, genetic studies are ongoing to unravel the missing heritability. By sequencing panels including multiple dementia-related genes, we identified a novel likely pathogenic mutation in SORL1 in a pedigree including five members affected by AD. This loss of function mutation may lead to a reduction of SORL1 receptor, worsening amyloidogenic burden. As the contribution of SORL1 mutations to heritability of AD is presently not well established, we think that it is very important to signal new familial (likely) pathogenic SORL1 mutations in order to define the actual genetic involvement of SORL1 in AD pathogenesis.
bioRxiv (Cold Spring Harbor Laboratory) · 2020 · 2 citations · open access
Brain transcriptome analysis reveals subtle effects on mitochondrial function and iron homeostasis of mutations in the <i>SORL1</i> gene implicated in early onset familial Alzheimer’s disease
AbstractAbstract Background To prevent or delay the onset of Alzheimer’s disease (AD), we must understand its molecular basis. The great majority of AD cases arise sporadically with a late onset after 65 years of age (LOAD). However, rare familial cases of AD can occur due to dominant mutations in a small number of genes that cause an early onset prior to 65 years of age (EOfAD). As EOfAD and LOAD share similar pathologies and disease progression, analysis of EOfAD genetic models may give insight into both subtypes of AD. Sortilin-related receptor 1 ( SORL1 ) is genetically associated with both EOfAD and LOAD and provides a unique opportunity to investigate the relationships between both forms of AD. Currently, the role of SORL1 mutations in AD pathogenesis is unclear. Methods To understand the molecular consequences of SORL1 mutation, we performed targeted mutagenesis of the orthologous gene in zebrafish. We generated an EOfAD-like mutation, V1482Afs, and a putatively null mutation, to investigate whether EOfAD-like mutations in sorl1 display haploinsufficiency by acting through loss-of-function mechanisms. We performed mRNA-sequencing on whole brains comparing normal (wild type) fish with their siblings heterozygous for EOfAD-like or complete loss-of-function mutations in sorl1 or transheterozygous for these mutations. Differential gene expression and gene set enrichment analyses identified, respectively, changes in young adult zebrafish brain transcriptomes, and putative effects on neural subcellular functions. Results We identified subtle effects on expression of genes involved in energy production, mRNA translation and mTORC1 signalling in both the EOfAD-like and null mutant brains, implying that these effects are due to sorl1 haploinsufficiency. Surprisingly, we also observed changes to expression of genes occurring only in the EOfAD-mutation carrier brains, suggesting gain-of-function effects. Transheterozygosity for the EOfAD-like and null mutations (i.e. lacking wild type sorl1 ), caused apparent effects on iron homeostasis and other transcriptome changes distinct from the single-mutation heterozygous fish. Conclusions Our results provide insight into the possible early brain molecular effects of an EOfAD mutation in human SORL1 . Differential effects of heterozygosity and complete loss of normal SORL1 expression are revealed.
Cambridge University Press eBooks · 2022 · 0 citations
Repurposed Agents in Alzheimer’s Disease Drug Development
AbstractDrug repositioning refers to the development of a drug for an indication other that in the marketing authorisation and drug repurposing is the use of known drugs for new indications. Both repositioning and repurposing are opportunities to complement traditional drug development and may shorten the time for a drug to reach the patient. This chapter provides a detailed overview of the pharmacological, preclinical, clinical and epidemiological evidence for four drugs or drug classes currently considered as the highest priority candidates for repurposing in Alzheimer’s disease: fasudil, phenserine, antiviral drugs and glucagon-like peptide 1 (GLP-1) analogs. In addition, key considerations on the future of repurposing are provided, including the role of transcriptional approaches and targeting risk genes and growth factors.
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.
