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A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

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Wiseman, Frances K., Al-Janabi, Tamara, Hardy, John, Karmiloff-Smith, Annette, Nizetic, Dean, Tybulewicz, Victor L. J., Fisher, Elizabeth M. C., Strydom, André·2015·Nature Reviews Neuroscience
DOI 10.1038/nrn3983PMC PMC4678594
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Abstract

Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP)--an Alzheimer disease risk factor--although the possession of extra copies of other chromosome 21 genes may also play a part. Further study of the mechanisms underlying the development of Alzheimer disease in people with Down syndrome could provide insights into the mechanisms that cause dementia in the general population.

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Cited by

Sorted by citations

Authors
Wiseman, F. K., Al-Janabi, T., Hardy, J., Karmiloff-Smith, A., Nizetic, D., Tybulewicz, V. L. J., Fisher, E. M. C., & Strydom, A.
Affiliations
  • UCL Queen Square Institute of Neurology (GB)
  • National Institute for Medical Research (GB)
  • University College London (GB)
Corresponding author
Fisher, Elizabeth M. C.
ORCID
Venue
Nature Reviews Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2015-08-05
Volume
16
Issue
9
Pages
564-574
ISSN
  • 1471-003X (ISSN-L)
  • 1471-0048
DOI
10.1038/nrn3983
PMC
PMC4678594
OpenAlex
W1776172174
Cited by
562
References
17
Citations by year
2026: 29 · 2025: 58 · 2024: 42 · 2023: 40 · 2022: 75 · 2021: 69 · 2020: 75 · 2019: 50 · 2018: 45 · 2017: 42 · 2016: 34 · 2015: 3
FWCI
5.08
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature reviews. Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • BIROn (Birkbeck, University of London) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Spiral (Imperial College London) (submittedVersion)
Funders
  • Wellcome Trust (98328, 098330, 098330/Z/12/Z, 098327/Z/12/Z)
  • Francis Crick Institute (10194)
  • Alzheimer's Society
  • Alzheimer Society
  • Epilepsy Research UK
  • Ministry of Education - Singapore
  • Medical Research Council (U117527252)
  • Lee Kong Chian School of Medicine, Nanyang Technological University
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Down syndrome, early-onset Alzheimer's disease, amyloid precursor protein, neurodegeneration, dementia, genetic risk factors, Alzheimer disease pathogenesis
MeSH terms
Alzheimer Disease, Down Syndrome, Humans, Amyloid beta-Peptides, Genetic Predisposition to Disease

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