ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2022
Impact of increased APP gene dose in Down syndrome and the Dp16 mouse model.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 54 citations in OpenAlex.
- Duplication-based genetic dissection of the Down syndrome critical region reveals its complex functional organization.G3 (Bethesda, Md.) · 2026Article
- A Researcher's guide to rodent models of Down syndrome: Recent insights and translational perspectives.STAR protocols · 2026Review
- Considerations for the selection and phenotyping of mouse models for the study of Alzheimer's disease.STAR protocols · 2026Review
- Age-related behavioral and molecular landmarks in new mouse models for studying Alzheimer's disease in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Alzheimer's disease: from molecular pathways to therapies.Molecular biomedicine · 2026Review
- Use of anti-amyloid-β monoclonal antibodies in persons with Down syndrome Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Impaired BDNF-TrkB trafficking and signalling in Down syndrome basal forebrain neurons.Cell death & disease · 2026Article
- Intracerebral age-independent reduction of endothelium-dependent hyperpolarization and nitric oxide signalling in the Dp16 mouse model of Down syndrome.The Journal of physiology · 2026Article
- Stereology with OPEN-Stereo: low-cost, accessible, and accurate cellular quantification.Scientific reports · 2025Article
- Toward a Unified Framework in Molecular Neurobiology of Alzheimer's Disease: Revisiting the Pathophysiological Hypotheses.Molecular neurobiology · 2025Review
- Tau pathology differs by sex in Alzheimer's disease in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The history of Down syndrome-associated Alzheimer's disease; past, present, and future.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome-Alzheimer's disease.Acta neuropathologica · 2025Article
- Antisense oligonucleotides directed against App and Rab5 normalized endosomal Rab activity and reversed DS-AD-linked degenerative phenotypes in the Dp16 mouse model of Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Hyperactivation of RAB5 disrupts the endosomal Rab cascade leading to endolysosomal dysregulation in Down syndrome: A necessary role for increased APP gene dose.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Plasma p-tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Copy number normalization distinguishes differential signals driven by copy number differences in ATAC-seq and ChIP-seq.BMC genomics · 2025Article
- Reduction of Cystatin B results in increased cathepsin B activity in disomic but not Trisomy 21 human cellular and mouse models.PloS one · 2025Article
- Transmembrane and coiled-coil 2 associates with Alzheimer's disease pathology in the human brain.Brain pathology (Zurich, Switzerland) · 2025Article
- γ-Secretase Modulator BPN15606 Reduced Aβ42 and Aβ40 and Countered Alzheimer-Related Pathologies in a Mouse Model of Down Syndrome.Annals of neurology · 2024Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
introductionPeople with Down syndrome (DS) are predisposed to Alzheimer's disease (AD). The amyloid hypothesis informs studies of AD. In AD-DS, but not sporadic AD, increased APP copy number is necessary, defining the APP gene dose hypothesis. Which amyloid precursor protein (APP) products contribute needs to be determined.
methodsBrain levels of full-length protein (fl-hAPP), C-terminal fragments (hCTFs), and amyloid beta (Aβ) peptides were measured in DS, AD-DS, non-demented controls (ND), and sporadic AD cases. The APP gene-dose hypothesis was evaluated in the Dp16 model.
resultsDS and AD-DS differed from ND and AD for all APP products. In AD-DS, Aβ42 and Aβ40 levels exceeded AD. APP products were increased in the Dp16 model; increased APP gene dose was necessary for loss of vulnerable neurons, tau pathology, and activation of astrocytes and microglia. DISCUSSION: Increases in APP products other than Aβ distinguished AD-DS from AD. Deciphering AD-DS pathogenesis necessitates deciphering which APP products contribute and how.
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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 Socratic graph.