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Cited by 105Down syndrome and intellectual disability researchDementia and Cognitive Impairment ResearchAlzheimer's disease research and treatments

Further understanding the connection between Alzheimer's disease and Down syndrome

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Snyder, Heather M., Bain, Lisa J., Brickman, Adam M., Carrillo, Maria C., Esbensen, Anna J., Espinosa, Joaquin M., Fernandez, Fabian, Fortea, Juan +16 more·2020·Alzheimer's & Dementia
DOI 10.1002/alz.12112PMC PMC8865308
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Abstract

Improved medical care of individuals with Down syndrome (DS) has led to an increase in life expectancy to over the age of 60 years. In conjunction, there has been an increase in age‐related co‐occurring conditions including Alzheimer's disease (AD). Understanding the factors that underlie symptom and age of clinical presentation of dementia in people with DS may provide insights into the mechanisms of sporadic and DS‐associated AD (DS‐AD). In March 2019, the Alzheimer's Association, Global Down Syndrome Foundation and the LuMind IDSC Foundation partnered to convene a workshop to explore the state of the research on the intersection of AD and DS research; to identify research gaps and unmet needs; and to consider how best to advance the field. This article provides a summary of discussions, including noting areas of emerging science and discovery, considerations for future studies, and identifying open gaps in our understanding for future focus.

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  • Some genes triplicated in Dp16 mice, including Dyrk1a, Usp25, S100b, Rcan1, and the Ifnrs, could contribute to cognitive dysfunction.

    “indicating that some genes triplicated in Dp16 mice could contribute to cognitive dysfunction, including Dyrk1a, Usp25, S100b, Rcan1, and the Ifnrs.”

    From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [16]

    In “Intersection of AD and DS: Commonalities and Differences” (page unavailable), the paper identifies DYRK1A, RCAN, S100B, and interferon receptor genes as chromosome 21 genes whose increased dosage may affect disease-related mechanisms. It does not identify USP25 in that list or establish that these particular genes are triplicated in Dp16 mice and contribute to their cognitive dysfunction. Its References mention a Dp16 mouse study of memory deficits, but not that gene-specific link. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Some genes triplicated in Dp16 mice may have a protective role, attenuating some phenotypes observed in AD, including Bace2 and Cstb involved in Aβ processing and clearance.

    “This suggests that some genes triplicated in Dp16 mice may also have a protective role, attenuating some phenotypes observed in AD, including Bace2 and Cstb that are involved in Aβ processing and clearance.”

    From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [16]

    The ‘Intersection of AD and DS: Commonalities and Differences’ section (page unavailable) identifies CSTB and BACE2 as involved in Aβ processing and clearance and says genes besides APP may modulate its effects. It does not say that these genes protect Dp16 mice or attenuate AD phenotypes. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Many additional genes on HSA21 modulate processes that could contribute to AD pathology in DS.

    “However, many additional genes on HSA21 modulate processes that could contribute to AD pathology in DS.14,15,16”

    From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [16]

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Authors
Snyder, H. M., Bain, L. J., Brickman, A. M., Carrillo, M. C., Esbensen, A. J., Espinosa, J. M., Fernandez, F., Fortea, J., Hartley, S. L., Head, E., Hendrix, J., Kishnani, P. S., Lai, F., Lao, P., Lemere, C., Mobley, W., Mufson, E. J., Potter, H., Zaman, S. H., Granholm, A., Rosas, H. D., Strydom, A., Whitten, M. S., & Rafii, M. S.
Affiliations
  • Alzheimer's Association (US)
  • Independent Science Writer Elverson Pennsylvania USA
  • Columbia University (US)
  • Alzheimer's Association Medical & Scientific Relations Chicago Illinois USA
  • Cincinnati Children's Hospital Medical Center (US)
  • University of Colorado Anschutz (US)
  • University of Arizona (US)
  • Universitat Autònoma de Barcelona (ES)
  • University of Wisconsin–Madison (US)
  • University of California, Irvine (US)
  • LuMind IDSC Foundation Burlington Massachusetts USA
  • Duke University (US)
  • Harvard University (US)
  • Columbia University Irving Medical Center (US)
  • Brigham and Women's Hospital (US)
  • University of California San Diego (US)
  • Barrow Neurological Institute (US)
  • University of Cambridge (GB)
  • University of Denver (US)
  • Massachusetts General Hospital (US)
  • Department of Forensic and Neurodevelopmental Sciences Psychology and Neuroscience King's College London South London and the Maudsley NHS Foundation Trust LonDowns Consortium Institute of Psychiatry London UK
  • Global Down Syndrome Foundation (US)
  • University of Southern California (US)
Corresponding author
Snyder, Heather M.
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2020-06-16
Volume
16
Issue
7
Pages
1065-1077
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1002/alz.12112
PMC
PMC8865308
OpenAlex
W3035322587
Cited by
105
References
20
Citations by year
2026: 9 · 2025: 19 · 2024: 23 · 2023: 12 · 2022: 23 · 2021: 17 · 2020: 2
FWCI
2.26
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Alzheimer s & Dementia (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
Cure Alzheimer's Fund
Topics
  • 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
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
Alzheimer's disease, Down syndrome
MeSH terms
Alzheimer Disease, Down Syndrome, Humans, Amyloid beta-Peptides

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