Microbleeds and Cerebral Amyloid Angiopathy in the Brains of People with Down Syndrome with Alzheimer's Disease

Alex M. Helman, Morgan Siever, Katie L. McCarty, Ira T. Lott, Eric Doran, Erin L. Abner, Frederick A. Schmitt, Elizabeth Head

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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 languageEnglish
Pages (from-to)103-112
Number of pages10
JournalJournal of Alzheimer's Disease
Volume67
Issue number1
DOIs
StatePublished - 2019

Bibliographical note

Publisher Copyright:
© 2019 IOS Press and the authors. All rights reserved.

Funding

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/). 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/).

FundersFunder number
NIA/NIH
National Institutes of Health (NIH)
National Institute on AgingP50AG16573, U01AG051412, R01AG21912
National Institute on Aging
NIH National Institute of Child Health and Human Development National Center for Medical Rehabilitation ResearchHDR01064993
NIH National Institute of Child Health and Human Development National Center for Medical Rehabilitation Research
National Center for Advancing Translational Sciences (NCATS)UL1TR001414
National Center for Advancing Translational Sciences (NCATS)
University of California Irvine

    Keywords

    • Cerebral amyloid angiopathy
    • Prussian blue
    • microhemorrhages
    • trisomy 21

    ASJC Scopus subject areas

    • General Neuroscience
    • Clinical Psychology
    • Geriatrics and Gerontology
    • Psychiatry and Mental health

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