Abstract
Cerebrovascular pathology is a significant mediator in Alzheimer's disease (AD) in the general population. In people with Down syndrome (DS), the contribution of vascular pathology to dementia may play a similar role in age of onset and/or the rate of progression of AD. In the current study, we explored the extent of microbleeds (MBs) and the link between cerebral amyloid angiopathy (CAA) and MBs in the frontal cortex (FCTX) and occipital cortex (OCTX) in an autopsy series from individuals with DS (<40 years), DS with AD pathology (DSAD), sporadic AD, and control cases (2-83 years). Sections were immunostained against Aβ 1-40 and an adjacent section stained using Prussian blue for MBs. MBs were both counted and averaged in each case and CAA was scored based on previously published methods. MBs were more frequent in DS cases relative to controls but present to a similar extent as sporadic AD. This aligned with CAA scores, with more extensive CAA in DS relative to controls in both brain regions. CAA was also more frequent in DSAD cases relative to sporadic AD. We found CAA to be associated with MBs and that MBs increased with age in DS after 30 years of age in the OCTX and after 40 years of age in the FCTX. MB and CAA appear to be a significant contributors to the development of dementia in people with DS and are important targets for future clinical trials.
Original language | English |
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Pages (from-to) | 103-112 |
Number of pages | 10 |
Journal | Journal of Alzheimer's Disease |
Volume | 67 |
Issue number | 1 |
DOIs | |
State | Published - 2019 |
Bibliographical note
Funding Information:Moving forward, our data suggests that we need to strongly consider cerebrovascular pathologies when studying adults with DS. It is particularly important as we think about designing clinical trials in Funding was provided by NIH/NICHD HDR01064993 to EH/EA/FAS. Autopsy cases from UC Irvine was supported by NIH/NIA P50AG16573 (ITL, ED), NIA R01AG21912 (ED, ITL), and U01AG051412 (ITL, ED). We also want to thank the NIH NeuroBioBank for a subset of the autopsy cases used in this study (https://neurobiobank.nih.gov/).
Funding Information:
NIH/NICHD HDR01064993 to EH/EA/FAS. Autopsy cases from UC Irvine was supported by NIH/NIA P50AG16573 (ITL, ED), NIA R01AG21912 (ED, ITL), and U01AG051412 (ITL, ED).We also want to thank the NIH NeuroBioBank for a subset of the autopsy cases used in this study (https://neurobiobank.nih.gov/).
Publisher Copyright:
© 2019 IOS Press and the authors. All rights reserved.
Keywords
- Cerebral amyloid angiopathy
- Prussian blue
- microhemorrhages
- trisomy 21
ASJC Scopus subject areas
- Neuroscience (all)
- Clinical Psychology
- Geriatrics and Gerontology
- Psychiatry and Mental health