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Alzheimer's disease associated with Down syndrome: a genetic form of dementia
Open accessAbstract
Adults with Down syndrome develop the neuropathological hallmarks of Alzheimer's disease and are at very high risk of developing early-onset dementia, which is now the leading cause of death in this population. Diagnosis of dementia remains a clinical challenge because of the lack of validated diagnostic criteria in this population, and because symptoms are overshadowed by the intellectual disability associated with Down syndrome. In people with Down syndrome, fluid and imaging biomarkers have shown good diagnostic performances and a strikingly similar temporality of changes with respect to sporadic and autosomal dominant Alzheimer's disease. Most importantly, there are no treatments to prevent Alzheimer's disease, even though adults with Down syndrome could be an optimal population in whom to conduct Alzheimer's disease prevention trials. Unprecedented research activity in Down syndrome is rapidly changing this bleak scenario that will translate into disease-modifying therapies that could benefit other populations.
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“Studies suggest that the brain changes of Alzheimer's disease in people with Down syndrome are more common than these percentages indicate.92,93”
From 2023 Alzheimer's disease facts and figures (2023) · cites this paper as [93]
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In the citing paper
“Emerging research suggests that Alzheimer's brain changes in people with Down syndrome may be even more common than these percentages indicate.”
From 2024 Alzheimer's disease facts and figures (2024) · cites this paper as [100]
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“increased risk for early‐onset Alzheimer's disease (AD). 2”
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“Although the extra copy of the amyloid precursor protein (APP) gene increases the penetrance of AD in DS, 2 , 6”
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“By age 40 years, most individuals with DS will have developed Alzheimer’s disease (AD) pathology, characterised by the accumulation of amyloid-β plaques and neurofibrillary tau tangles (NFT) within the brain [17, 69].”
From Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome–Alzheimer’s disease (2025) · cites this paper as [17]
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“This relationship is observed across the AD continuum, including the asymptomatic phase in sporadic and genetic forms of AD.11,12,13,14”
From Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology (2024) · cites this paper as [14]
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Metadata
- Authors
- Fortea, J., Zaman, S. H., Hartley, S., Rafii, M. S., Head, E., & Carmona-Iragui, M.
- Affiliations
- Universitat Autònoma de Barcelona (ES)
- University of Cambridge (GB)
- University of Wisconsin–Madison (US)
- University of Southern California (US)
- University of California, Irvine (US)
- Corresponding author
- Fortea, Juan
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2021-11
- Volume
- 20
- Issue
- 11
- Pages
- 930-942
- ISSN
- 1474-4422 (ISSN-L)
- PMC
- PMC9387748
- OpenAlex
- W3205749467
- Cited by
- 357
- References
- 125
- Citations by year
- 2026: 66 · 2025: 121 · 2024: 83 · 2023: 48 · 2022: 36 · 2021: 3
- FWCI
- 7.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Generalitat de Catalunya
- Instituto de Salud Carlos III
- National Institutes of Health
- Roche España (BFF17-008, P30AG066519, PI18/00335, R01HD064993, U19AG068054)
- European Commission
- Fondation Jérôme Lejeune (1913, 2019B)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01AG031110, U01 AG051412, U01AG051406, U54 HD090256)
- Global Brain Health Institute (GBHI_ALZ-18-543740)
- European Regional Development Fund
- National Institute on Aging (1R01AG056850 - 01A1, R01AG061566, R21AG056974)
- Generalitat of Catalonia Department of Health (SLT006/17/00119)
- Fundació Víctor Grífols i Lucas
- Alzheimer's Association
- Societat Catalana de Pneumologia
- Fundació la Marató de TV3 (20141210)
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- Down syndrome, Alzheimer's disease, early-onset dementia, dementia diagnosis, fluid biomarkers, neuroimaging biomarkers, intellectual disability, Alzheimer's disease prevention, disease-modifying therapy
- MeSH terms
- Adult, Alzheimer Disease, Down Syndrome, Humans, Intellectual Disability, Biomarkers
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