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Brain Perivascular Macrophages Initiate the Neurovascular Dysfunction of Alzheimer Aβ Peptides
Park L, Uekawa K, Garcia-Bonilla L, Koizumi K, Murphy M, Pistik R, Younkin L, Younkin S et al.. Circulation research, 2017-05-17
Topic: Brain proteins, microglia and lab models
Rationale Increasing evidence indicates that alterations of the cerebral microcirculation may play a role in Alzheimer disease, the leading cause of late-life dementia. The amyloid-β peptide (Aβ), a key pathogenic factor in Alzheimer disease, induces profound alterations in neurovascular regulation through the innate immunity receptor CD36 (cluster of differentiation 36), which, in turn, activates a Nox2-containing NADPH oxidase, leading to cerebrovascular oxidative stress. Brain perivascular macrophages (PVM) located in the perivascular space, a major site of brain Aβ collection and clearance, are juxtaposed to the wall of intracerebral resistance vessels and are a powerful source of reactive oxygen species.
Key findings
- The amyloid-β peptide (Aβ), a key pathogenic factor in Alzheimer disease, induces profound alterations in neurovascular regulation through the innate immunity receptor CD36 (cluster of differentiation 36), which, in turn, activates a Nox2-containing NADPH oxidase, leading to cerebrovascular oxidative stress.
- Brain perivascular macrophages (PVM) located in the perivascular space, a major site of brain Aβ collection and clearance, are juxtaposed to the wall of intracerebral resistance vessels and are a powerful source of reactive oxygen species.
- Objective We tested the hypothesis that PVM are the main source of reactive oxygen species responsible for the cerebrovascular actions of Aβ and that CD36 and Nox2 in PVM are the molecular substrates of the effect.
- Methods and results Selective depletion of PVM using intracerebroventricular injection of clodronate abrogates the reactive oxygen species production and cerebrovascular dysfunction induced by Aβ applied directly to the cerebral cortex, administered intravascularly, or overproduced in the brain of transgenic mice expressing mutated forms of the amyloid precursor protein (Tg2576 mice).
Why it matters
In mice, removing the brain's perivascular macrophages — immune cells that sit along blood-vessel walls where amyloid-β collects — "abrogates the reactive oxygen species production and cerebrovascular dysfunction induced by Aβ," including in Tg2576 mice that overproduce it. The authors tested whether these cells, via CD36 and Nox2, are the main source of that vessel-damaging oxidative stress. This is mechanistic animal research; it does not test a treatment or show any benefit for patients.
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Study details
- Evidence strengthLow
How this study scored 52/100
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 (Circulation research) |
| Journal's citation record | 4 / 4 | Circulation Research: journal h-index 507 (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 | 2017 — 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 | 5 / 7 | Cited 261 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 23.7 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 4 / 6 | Cited 11.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 3 / 4 | Cited 112 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Costantino Iadecola: h-index 128 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Cornell University: institution h-index 1,649 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28515043) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
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Read the original
- DOI: 10.1161/circresaha.117.311054
- PubMed: 28515043
- Original source →
- Free full text: Circulation Research →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Park, L., Uekawa, K., Garcia-Bonilla, L., Koizumi, K., Murphy, M., Pistik, R., et al. (2017). Brain Perivascular Macrophages Initiate the Neurovascular Dysfunction of Alzheimer Aβ Peptides. Circulation research. https://doi.org/10.1161/circresaha.117.311054
Vancouver
Park L, Uekawa K, Garcia-Bonilla L, Koizumi K, Murphy M, Pistik R, et al. Brain Perivascular Macrophages Initiate the Neurovascular Dysfunction of Alzheimer Aβ Peptides. Circulation research. 2017. doi:10.1161/circresaha.117.311054. PMID: 28515043.
BibTeX
@article{park2017-28515043,
author = {Park, L. and Uekawa, K. and Garcia-Bonilla, L. and Koizumi, K. and Murphy, M. and Pistik, R. and Younkin, L. and Younkin, S. and others},
title = {{Brain Perivascular Macrophages Initiate the Neurovascular Dysfunction of Alzheimer Aβ Peptides}},
journal = {Circulation research},
year = {2017},
doi = {10.1161/circresaha.117.311054},
pmid = {28515043},
url = {https://doi.org/10.1161/circresaha.117.311054}
}
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