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Cited by 105Down syndrome and intellectual disability researchAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

The DOI matches its Crossref record; 60 of the 61 references it cites were found in a registry or an index.

Cerebrovascular pathology in Down syndrome and Alzheimer disease

Open access
Head, Elizabeth, Phelan, Michael J., Doran, Eric, Kim, Ronald C., Poon, Wayne W., Schmitt, Frederick A., Lott, Ira T.·2017·Acta Neuropathologica Communications
DOI 10.1186/s40478-017-0499-4PMC PMC5709935
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Abstract

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD) with age. Typically, by age 40 years, most people with DS have sufficient neuropathology for an AD diagnosis. Interestingly, atherosclerosis and hypertension are atypical in DS with age, suggesting the lack of these vascular risk factors may be associated with reduced cerebrovascular pathology. However, because the extra copy of APP leads to increased beta-amyloid peptide (Aβ) accumulation in DS, we hypothesized that there would be more extensive and widespread cerebral amyloid angiopathy (CAA) with age in DS relative to sporadic AD. To test this hypothesis CAA, atherosclerosis and arteriolosclerosis were used as measures of cerebrovascular pathology and compared in post mortem tissue from individuals with DS (n = 32), sporadic AD (n = 80) and controls (n = 37). CAA was observed with significantly higher frequencies in brains of individuals with DS compared to sporadic AD and controls. Atherosclerosis and arteriolosclerosis were rare in the cases with DS. CAA in DS may be a target for future interventional clinical trials.

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Crossref · 10.1186/s40478-017-0499-4

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Figures

Fig. 1 Percentage of autopsy cases by severity of cerebrovascular outcome and cohort. Percentages for Atherosclerosis, Arteriolosclerosis, and Cerebral Amyloid Angiopathy (CAA) add to 100% within each cohort, separately. More moderate and severe CAA findings were associated particularly with the DS cohort
Fig. 1 Percentage of autopsy cases by severity of cerebrovascular outcome and cohort. Percentages for Atherosclerosis, Arteriolosclerosis, and Cerebral Amyloid Angiopathy (CAA) add to 100% within each cohort, separately. More moderate and severe CAA findings were associated particularly with the DS cohortCC BY · PubMed Central
Fig. 2 Age at autopsy across the three cohorts (DS, AD, Ctrl) showing that the DS cases were younger than the AD and Control (Ctrl) cases. Individual data points are shown in open circles, group means in solid, red circles. Error bars show plus-and-minus one standard deviation from the mean
Fig. 2 Age at autopsy across the three cohorts (DS, AD, Ctrl) showing that the DS cases were younger than the AD and Control (Ctrl) cases. Individual data points are shown in open circles, group means in solid, red circles. Error bars show plus-and-minus one standard deviation from the meanCC BY · PubMed Central
Fig. 3 Arteriolosclerosis as a function of age in DS, AD and Controls. Individual data points shown as open circles, group means as filled circles. Error bars show plus-and-minus one standard deviation from the mean
Fig. 3 Arteriolosclerosis as a function of age in DS, AD and Controls. Individual data points shown as open circles, group means as filled circles. Error bars show plus-and-minus one standard deviation from the meanCC BY · PubMed Central
Fig. 4 Atherosclerosis as a function of age in DS, AD and Controls. Individual data points shown as open circles, group means as filled circles. Error bars show plus-and-minus one standard deviation from the mean
Fig. 4 Atherosclerosis as a function of age in DS, AD and Controls. Individual data points shown as open circles, group means as filled circles. Error bars show plus-and-minus one standard deviation from the meanCC BY · PubMed Central
Fig. 5 Probability of CAA severity as a function of age-at-autopsy in DS cohort. Error bars show the upper and lower limits of the 95% confidence interval. The number of DS cases with no or mild CAA decreases with age. The number of people with DS with moderate CAA remains relatively stable but the numbers of cases with severe CAA increases with age
Fig. 5 Probability of CAA severity as a function of age-at-autopsy in DS cohort. Error bars show the upper and lower limits of the 95% confidence interval. The number of DS cases with no or mild CAA decreases with age. The number of people with DS with moderate CAA remains relatively stable but the numbers of cases with severe CAA increases with ageCC BY · PubMed Central
Fig. 6 Probability curves for CAA severity based on age-at-autopsy in DS cohort. The age at which CAA shifts from mild, to moderate to severe are estimated based on age. Moderate to severe findings were more likely at upper ages
Fig. 6 Probability curves for CAA severity based on age-at-autopsy in DS cohort. The age at which CAA shifts from mild, to moderate to severe are estimated based on age. Moderate to severe findings were more likely at upper agesCC BY · PubMed Central

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  1. R_Core_Team (2016) A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna

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Metadata

Authors
Head, E., Phelan, M. J., Doran, E., Kim, R. C., Poon, W. W., Schmitt, F. A., & Lott, I. T.
Affiliations
  • University of Kentucky (US)
  • University of California, Irvine (US)
Corresponding author
Head, Elizabeth
ORCID
Venue
Acta Neuropathologica Communications
Publisher
Springer Science and Business Media LLC
Published
2017-12
Volume
5
Issue
1
Pages
93-93
ISSN
2051-5960 (ISSN-L)
DOI
10.1186/s40478-017-0499-4
PMC
PMC5709935
OpenAlex
W2771929031
Cited by
105
References
61
Citations by year
2026: 9 · 2025: 22 · 2024: 18 · 2023: 9 · 2022: 12 · 2021: 15 · 2020: 8 · 2019: 8 · 2018: 4
FWCI
5.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • UKnowledge (University of Kentucky) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institute on Aging (P50AG16573, R01AG21912)
  • National Institute of Child Health and Human Development (R01HD065160, R01HD064993)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Down syndrome, Alzheimer's disease, cerebral amyloid angiopathy, cerebrovascular pathology, atherosclerosis, arteriolosclerosis, amyloid-beta deposition, vascular risk factors, postmortem brain
MeSH terms
Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Down Syndrome, Female, Humans, Male, Middle Aged, Probability, Cohort Studies, Cerebral Amyloid Angiopathy, Atherosclerosis, Arteriolosclerosis

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