ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
Early blood immune molecular alterations in cynomolgus monkeys with a PSEN1 mutation causing familial Alzheimer's disease.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Modeling Tau-Mediated Pathology in Monkey Brain Slices.Biology · 2026Article
- A Comparative Study of Plasma Biomarkers of Neurodegeneration in Rhesus Monkeys (bioRxiv : the preprint server for biology · 2026Article
- Identification of putative kidney-derived proteins in plasma using nanoparticle enrichment.Molecular omics · 2026Article
- Genetically Modified Primate Models for Brain Disorder Research.Neuroscience bulletin · 2026Review
- Review
- ATM deficiency drives phenotypic diversity and Purkinje cell degeneration in a macaque model of ataxia-telangiectasia.Cell reports. Medicine · 2025Article
- Integrating neuroinflammation biomarkers into the ATN(X) framework: Advances in Alzheimer's pathogenesis, diagnosis, and insights from non-human primate models.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Animal models of Alzheimer's disease: Current strategies and new directions.Zoological research · 2024Review
- Early blood immune molecular alterations in cynomolgus monkeys with a PSEN1 mutation causing familial Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
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22 authors.
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Abstract
introductionMore robust non-human primate models of Alzheimer's disease (AD) will provide new opportunities to better understand the pathogenesis and progression of AD.
methodsWe designed a CRISPR/Cas9 system to achieve precise genomic deletion of exon 9 in cynomolgus monkeys using two guide RNAs targeting the 3' and 5' intron sequences of PSEN1 exon 9. We performed biochemical, transcriptome, proteome, and biomarker analyses to characterize the cellular and molecular dysregulations of this non-human primate model.
resultsWe observed early changes of AD-related pathological proteins (cerebrospinal fluid Aβ DISCUSSION: PSEN1 mutant cynomolgus monkeys recapitulate AD-related pathological protein changes, and reveal early alterations in blood immune signaling. Thus, this model might mimic AD-associated pathogenesis and has potential utility for developing early diagnostic and therapeutic interventions. HIGHLIGHTS: A dual-guide CRISPR/Cas9 system successfully mimics AD PSEN1-ΔE9 mutation by genomic excision of exon 9. PSEN1 mutant cynomolgus monkey-derived fibroblasts exhibit disrupted PSEN1 endoproteolysis and increased Aβ secretion. Blood transcriptome and proteome profiling implicate early inflammatory and immune molecular dysregulation in juvenile PSEN1 mutant cynomolgus monkeys. Cerebrospinal fluid from juvenile PSEN1 mutant monkeys recapitulates early changes of AD-related pathological proteins (increased Aβ
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