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.

Document Type

Article

Publication Date

12-1-2017

Notes/Citation Information

Published in Acta Neuropathologica Communications, v. 5, 93 p. 1-9.

© The Author(s). 2017

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Digital Object Identifier (DOI)

https://doi.org/10.1186/s40478-017-0499-4

Funding Information

The US National Institutes of Health supported this study through the following grants: National Institutes on Aging P50AG16573 (E.D., R C.K., W.W.P., I.T.L.); National Institutes on Aging R01AG 21,912 (E.D., I.T.L.); National Institutes on Aging R01HD065160 (E.D., I.T.L.); National Institutes on Child Health and Development R01HD064993 (E.H., F.A.S.).

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