Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down’s syndrome
Abstract
One hundred brains of patients with Down's syndrome (DS) who died in institutions for chronic care were examined for clinicopathological correlation of Alzheimer's disease. Fifty-one were below and 49 were above age 30 years at death. Tissues from the right, prefrontal, and hippocampal cortices were processed for microscopy using H&E and Bodian-periodic acid-Schiff impregnation. Morphometric evaluations of plaques and tangles were carried out. Plaques or plaques and tangles were found in the brains of 56 patients with DS, 7 below age 30 and 49 above that age. A history of dementia was evident in the medical records of 15 of these patients; of these only 2 were below the age of 30. The brains of the patients with DS who also had clinical dementia had more than twenty plaques or plaques and tangles per 1.5 X 10(6) micron 2 of cortex. The numbers of plaques and tangles found in the brains of the patients with DS above the age of 30 greatly increased with age but varied from brain to brain. These observations suggest a correlation among dementia, the density of plaques and tangles, and age. All 100 brains studied showed early arrest of brain growth and brain atrophy, a condition that may have been due to prenatal arrest of neurogenesis mainly in the granular cell layers, prenatal and postnatal arrest of synaptogenesis, and early aging. Plaques and tangles developed twenty to thirty years earlier and dementia was clinically detected at least three times more frequently (20 to 30%) in DS than it is known to occur in the non-DS population.
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Virtually all people with full trisomy 21 are expected to develop the pathophysiological changes of Alzheimer's disease by their early to mid-40s.
“Because virtually all people with full trisomy 21 are expected to develop the pathophysiological changes of AD by their earyl to mid‐40's, this longitudinal design provides a unique opportunity to track physiological and cognitive changes through the clinically asymptomatic preclinical to the clinical stages of dementia.”
From The Alzheimer's Biomarker Consortium–Down Syndrome (ABC‐DS): A 10‐year report (2025) · cites this paper as [3]
Most adults with Down syndrome will have the neuropathologies characteristic of Alzheimer's disease by their early to mid-40s.
“In fact, most adults with DS will have the neuropathologies characteristic of AD by the time they reach their early to mid‐40s that anticipates further progression some years or decades later. 3 , 4 , 5 , 6”
From The Alzheimer's Biomarker Consortium–Down Syndrome (ABC‐DS): A 10‐year report (2025) · cites this paper as [3]
APP gene duplications resulting from trisomy of chromosome 21 (Down's Syndrome) result in near-complete penetrance of AD neuropathology and increased incidence of dementia by age 30-40y.
“APP gene duplications that result from trisomy of chromosome 21 (Down’s Syndrome) result in near-complete penetrance of AD neuropathology and increased incidence of dementia by age 30–40y [250, 251]”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [250]
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- Authors
- Wisniewski, K. E., Wisniewski, H. M., & Wen, G. Y.
- Affiliations
- New York State Office for People With Developmental Disabilities (US)
- Corresponding author
- Wisniewski, K. E.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 1985-03
- Volume
- 17
- Issue
- 3
- Pages
- 278-282
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2041789591
- Cited by
- 1,159
- References
- 30
- Citations by year
- 2026: 9 · 2025: 27 · 2024: 31 · 2023: 18 · 2022: 32 · 2021: 33 · 2020: 48 · 2019: 31 · 2018: 23 · 2017: 30 · 2016: 32 · 2015: 40 · 2014: 33 · 2013: 30 · 2012: 26
- FWCI
- 32.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Down syndrome, Alzheimer's disease, dementia, neuropathology, amyloid plaques, neurofibrillary tangles, clinicopathological correlation, brain atrophy, synaptogenesis, neurogenesis, hippocampus, prefrontal cortex
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Alzheimer Disease, Amyloid, Brain, Child, Down Syndrome, Humans, Middle Aged, Neurofibrils, Organ Size
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