Alzheimer's disease in Down's syndrome: Clinicopathologic studies
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Clinical and neuropathologic evidence points to the development of Alzheimer's disease (AD) in seven Down's syndrome patients above age 40. Dementia was observed in these patients over periods of 2.5 to 9.2 years. The first clinical sign of AD, visual memory loss, was succeeded by impaired learning capacity and decreased occupational and social functioning, and culminated in seizures and urinary incontinence. The morphometric observations of the brains of these seven patients with AD showed that the numbers of plaques and tangles exceeded 20 per 1.5 X 10(6) microns2 area, in both the prefrontal and hippocampal cortices. Plaques and tangles were also evident in the basal ganglia, thalamus, hypothalamus, and midbrain. In addition, we found that four of the seven brains showed small strokes, and five of the seven amyloid angiopathy. This study also indicates that by longitudinal neuropsychological evaluations and lab tests, which exclude other causes of dementia, the diagnosis of AD can be made even in severely and profoundly retarded patients.
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Individuals with Down syndrome (T21) are strongly predisposed to Alzheimer's disease, with nearly all exhibiting AD-related neuropathological features by age ∼40 and highly variable onset of dementia thereafter.
“Individuals with Down syndrome (DS), caused by trisomy of chromosome 21 (chr21, T21), are strongly predisposed to Alzheimer’s disease (AD), due to triplication of the APP gene, with ∼100% penetrance of AD brain pathology by age 40 and variable onset of dementia thereafter.”
From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [7]
The Abstract reports Alzheimer’s pathology in seven Down syndrome patients older than 40, and the Results (Morphometric methods) give varying ages of cognitive-symptom onset, from 43.2 to 57.6 years. The study does not establish that nearly all people with Down syndrome have AD pathology by age 40; its seven patients were older than 40 and had clinical AD. Our copy also does not attribute the predisposition to APP gene triplication. (LLM, conf=0.88)
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- Neurology K. E. Wisniewski, A. J. Dalton, D. R. Crapper McLachlan, et al. Alzheimer's disease in Down's syndrome: Clinicopathologic studies This information is current as of July 1, 1985 Services Updated Information & http://n.neurology.org/content/35/7/957.full including high resolution figures, can be found at: Citations s http://n.neurology.org/content/35/7/957.full##otherarticle This article has been cited by 7 HighWire-hosted articles: Permissions & Licensing ssions http://www.neurology.org/about/about_the_journal#permi (figures,tables) or in its entirety can be found online at: Information about reproducing this article in parts Reprints http://n.neurology.org/subscribers/advertise Information about ordering reprints can be found online: 1526-632X. American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 1985 by the ® is the official journal of the American Academy of Neurology. Published Neurology
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- Authors
- Wisniewski, K. E., Dalton, A. J., McLachlan, D. R. C., Wen, G. Y., & Wisniewski, H. M.
- Affiliations
- University of Toronto (CA)
- New York State Office of Mental Retardation and Developmental Disabilities, Institute for Basic Resrarch in Developmental Disabilities, Staten Island, NY (Drs Wisiniewski, Wen, and H.M. Wisniewski); Surrey Place Center (Drs. Dalton and Crapper McLachlan). and the University of Toronto (Dr. Crapper McLachlan). toronto. Ontario, Candada.
- Venue
- Neurology
- Published
- 1985-07
- Volume
- 35
- Issue
- 7
- Pages
- 957-957
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2147029696
- Cited by
- 417
- References
- 2
- Citations by year
- 2026: 3 · 2025: 16 · 2024: 12 · 2023: 6 · 2022: 9 · 2021: 11 · 2020: 7 · 2019: 9 · 2018: 10 · 2017: 8 · 2016: 11 · 2015: 15 · 2014: 17 · 2013: 14 · 2012: 12
- FWCI
- 15.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Toronto
- 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, dementia, amyloid plaques, neurofibrillary tangles, brain morphometry, amyloid angiopathy, stroke, learning disabilities, seizures, urinary incontinence
- MeSH terms
- Adult, Alzheimer Disease, Brain, Down Syndrome, Female, Humans, Male, Middle Aged
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