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Microbleeds and Cerebral Amyloid Angiopathy in the Brains of People with Down Syndrome with Alzheimer's Disease
Helman AM, Siever M, McCarty KL, Lott IT, Doran E, Abner EL, Schmitt FA, Head E.. Journal of Alzheimer's disease : JAD, 2019-01-01
Topic: Brain proteins, microglia and lab models
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 Aβ1 - 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.
Key findings
- Cerebrovascular pathology is a significant mediator in Alzheimer's disease (AD) in the general population.
- 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.
Why it matters
In autopsy brain tissue, small bleeds and cerebral amyloid angiopathy were more common in Down syndrome and appeared to contribute to dementia. The authors say these are targets for future clinical trials, so no treatment is established yet.
Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease : JAD) |
| Journal's citation record | 2 / 4 | Journal of Alzheimer s Disease: journal h-index 218 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 48 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.3 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 2 / 6 | Cited 2.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 25 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Elizabeth Head: h-index 98 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of California, Irvine: institution h-index 1,195 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30452414) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Helman, A. M., Siever, M., McCarty, K. L., Lott, I. T., Doran, E., Abner, E. L., et al. (2019). Microbleeds and Cerebral Amyloid Angiopathy in the Brains of People with Down Syndrome with Alzheimer's Disease. Journal of Alzheimer's disease : JAD. https://doi.org/10.3233/jad-180589
Vancouver
Helman AM, Siever M, McCarty KL, Lott IT, Doran E, Abner EL, et al. Microbleeds and Cerebral Amyloid Angiopathy in the Brains of People with Down Syndrome with Alzheimer's Disease. Journal of Alzheimer's disease : JAD. 2019. doi:10.3233/jad-180589. PMID: 30452414.
BibTeX
@article{helman2019-30452414,
author = {Helman, A. M. and Siever, M. and McCarty, K. L. and Lott, I. T. and Doran, E. and Abner, E. L. and Schmitt, F. A. and Head, E.},
title = {{Microbleeds and Cerebral Amyloid Angiopathy in the Brains of People with Down Syndrome with Alzheimer's Disease}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2019},
doi = {10.3233/jad-180589},
pmid = {30452414},
url = {https://doi.org/10.3233/jad-180589}
}
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