Evidence map›Paper›PMID 29945247›Full record

ArticleBrain : a journal of neurology2018

Trisomy of human chromosome 21 enhances amyloid-β deposition independently of an extra copy of APP.

Frances K Wiseman, Laura J Pulford, Chris Barkus, Fan Liao, Erik Portelius, Robin Webb, Lucia Chávez-Gutiérrez, Karen Cleverley, Sue Noy, Olivia Sheppard and 20 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 86 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 3 pooled it
15.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 3 syntheses or guidelines pooled it, 133 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. 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 · 2026
    Review
  11. bioRxiv : the preprint server for biology · 2026
    Article
  12. Review
  13. Article
  14. The Hallmarks of Aneuploidy in Cancer and Congenital Syndromes.Annual review of genomics and human genetics · 2025
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 9 institutions in 4 countries.

Frances K WisemanDepartment of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG UK.
Laura J PulfordDepartment of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG UK.
Chris BarkusDepartment of Experimental Psychology, University of Oxford, Oxford, OX1 3PH, UK.
Fan LiaoDepartment of Neurology, Washington University School of Medicine, St Louis, Missouri, 63110, USA.
Erik PorteliusDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, S-405 30, Sweden.
Robin WebbSanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, 40507, USA.
Lucia Chávez-GutiérrezVIB-KU Leuven Center for Brain and Disease Research, VIB-Leuven 3000, Center for Human Genetics, Universitaire Ziekenhuizen and LIND, KU Leuven, Leuven, Belgium.
Karen CleverleyDepartment of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG UK.
Sue NoyDepartment of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG UK.
Olivia SheppardDepartment of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG UK.
Toby CollinsDepartment of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG UK.
Caroline PowellMRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London W1W 7FF, UK.
Claire J SarellMRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London W1W 7FF, UK.
Matthew RickmanDepartment of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG UK.
Xun ChoongDepartment of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG UK.
Justin L ToshDepartment of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG UK.
Carlos SiganporiaDepartment of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG UK.
Heather T WhittakerDepartment of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG UK.
Floy StewartDepartment of Neurology, Washington University School of Medicine, St Louis, Missouri, 63110, USA.
Maria SzarugaVIB-KU Leuven Center for Brain and Disease Research, VIB-Leuven 3000, Center for Human Genetics, Universitaire Ziekenhuizen and LIND, KU Leuven, Leuven, Belgium.
London Down syndrome consortium
Michael P MurphySanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, 40507, USA.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, S-405 30, Sweden.
Bart de StrooperVIB-KU Leuven Center for Brain and Disease Research, VIB-Leuven 3000, Center for Human Genetics, Universitaire Ziekenhuizen and LIND, KU Leuven, Leuven, Belgium.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, S-405 30, Sweden.
David BannermanDepartment of Experimental Psychology, University of Oxford, Oxford, OX1 3PH, UK.
David M HoltzmanDepartment of Neurology, Washington University School of Medicine, St Louis, Missouri, 63110, USA.
Victor L J TybulewiczThe LonDownS Consortium, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Denmark Hill, London, SE5 8AF, UK.
Elizabeth M C FisherDepartment of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG UK.
LonDownS Consortium
University College London · GBUniversity of Gothenburg · SEWashington University in St. Louis · USImperial College London · GBKing's College London · GBUniversity of Kentucky · USUniversity of Oxford · GBVIB-KU Leuven Center for Brain & Disease Research · BEMRC Prion Unit · GB

Funding

Medical Research Council G0400074Medical Research Council G0502157Medical Research Council G0601056Medical Research Council G0900652Medical Research Council G1100540Medical Research Council MR/S005145/1Medical Research Council U117527252Wellcome Trust 098330/Z/12/ZWellcome Trust FC001194
6 · The paper itself

Abstract

Down syndrome, caused by trisomy of chromosome 21, is the single most common risk factor for early-onset Alzheimer's disease. Worldwide approximately 6 million people have Down syndrome, and all these individuals will develop the hallmark amyloid plaques and neurofibrillary tangles of Alzheimer's disease by the age of 40 and the vast majority will go on to develop dementia. Triplication of APP, a gene on chromosome 21, is sufficient to cause early-onset Alzheimer's disease in the absence of Down syndrome. However, whether triplication of other chromosome 21 genes influences disease pathogenesis in the context of Down syndrome is unclear. Here we show, in a mouse model, that triplication of chromosome 21 genes other than APP increases amyloid-β aggregation, deposition of amyloid-β plaques and worsens associated cognitive deficits. This indicates that triplication of chromosome 21 genes other than APP is likely to have an important role to play in Alzheimer's disease pathogenesis in individuals who have Down syndrome. We go on to show that the effect of trisomy of chromosome 21 on amyloid-β aggregation correlates with an unexpected shift in soluble amyloid-β 40/42 ratio. This alteration in amyloid-β isoform ratio occurs independently of a change in the carboxypeptidase activity of the γ-secretase complex, which cleaves the peptide from APP, or the rate of extracellular clearance of amyloid-β. These new mechanistic insights into the role of triplication of genes on chromosome 21, other than APP, in the development of Alzheimer's disease in individuals who have Down syndrome may have implications for the treatment of this common cause of neurodegeneration.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBrainDisease Models, AnimalDown SyndromeFemaleHumansMaleMiceMice, Inbred C57BLNeurofibrillary TanglesPlaque, AmyloidTrisomyAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAPP protein, human

Identifiers

PMID29945247
PMCPMC6061702
OpenAlexW2810011474

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.