APOE, vascular pathology, and the AD brain
Yip AG, McKee AC, Green RC, Wells J, Young H, Cupples LA, Farrer LA.. Neurology, 2005-07-01
Topic: Amyloid, tau and blood-test diagnosis
Objective To use neuropathologic data to examine the association between APOE genotype and cerebrovascular lesions commonly found in Alzheimer disease (AD), as well as neuritic senile plaque (SP) and neurofibrillary tangle (NFT) burden. Methods The sample comprised brains from 96 men and 3 women who fulfilled NIA-Reagan criteria for intermediate to high likelihood of AD. Region-specific and global measures of gross cerebrovascular disease, arteriolosclerosis, white matter lesions, microinfarcts, amyloid angiopathy, neuritic SP, and NFT burden were compared among those who had at least one APOE-epsilon4 vs those who did not. Pairwise rank-order correlations between measures were calculated. The association between APOE epsilon4 status and measures of vascular and AD pathology, adjusting for age at death, sex, brain weight, and Braak stage, were evaluated. Results APOE-epsilon4 was not associated with gross cerebrovascular pathology. Compared to those who were negative, brains from epsilon4 individuals had a greater degree of small vessel arteriolosclerosis (p = 0.04) and perivascular macrophage infiltration (p = 0.06), but not other markers of small vessel disease or white matter myelin loss. Microinfarcts in the deep nuclei were associated with epsilon4 (p = 0.009), whereas cortical and subcortical microinfarcts were not. There was a trend toward association between APOE genotype and amyloid angiopathy (p = 0.08), and epsilon4 was associated with neuritic SP burden, but not NFT. Conclusion APOE-epsilon4 is associated with small vessel arteriolosclerosis, microinfarcts of the deep nuclei, neuritic senile plaque density, and amyloid angiopathy in patients with autopsy-proven Alzheimer disease (AD). These results suggest a role for epsilon4 in some of the microvascular changes commonly found in AD and are consistent with a potential amyloidogenic role for epsilon4.
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APA 7th
Yip, A. G., McKee, A. C., Green, R. C., Wells, J., Young, H., Cupples, L. A., et al. (2005). APOE, vascular pathology, and the AD brain. Neurology. https://doi.org/10.1212/01.wnl.0000168863.49053.4d
Vancouver
Yip AG, McKee AC, Green RC, Wells J, Young H, Cupples LA, et al. APOE, vascular pathology, and the AD brain. Neurology. 2005. doi:10.1212/01.wnl.0000168863.49053.4d. PMID: 16043796.
BibTeX
@article{yip2005-16043796,
author = {Yip, A. G. and McKee, A. C. and Green, R. C. and Wells, J. and Young, H. and Cupples, L. A. and Farrer, L. A.},
title = {{APOE, vascular pathology, and the AD brain}},
journal = {Neurology},
year = {2005},
doi = {10.1212/01.wnl.0000168863.49053.4d},
pmid = {16043796},
url = {https://doi.org/10.1212/01.wnl.0000168863.49053.4d}
}
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 7 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.
Key findings
- Results APOE-epsilon4 was not associated with gross cerebrovascular pathology.
- Compared to those who were negative, brains from epsilon4 individuals had a greater degree of small vessel arteriolosclerosis (p = 0.04) and perivascular macrophage infiltration (p = 0.06), but not other markers of small vessel disease or white matter myelin loss.
- Microinfarcts in the deep nuclei were associated with epsilon4 (p = 0.009), whereas cortical and subcortical microinfarcts were not.
- There was a trend toward association between APOE genotype and amyloid angiopathy (p = 0.08), and epsilon4 was associated with neuritic SP burden, but not NFT.
- Conclusion APOE-epsilon4 is associated with small vessel arteriolosclerosis, microinfarcts of the deep nuclei, neuritic senile plaque density, and amyloid angiopathy in patients with autopsy-proven Alzheimer disease (AD).
Why it matters
In brains from people who met criteria for intermediate to high likelihood of Alzheimer's disease, APOE epsilon4 was not associated with gross cerebrovascular pathology but was associated with greater small vessel arteriolosclerosis and with microinfarcts in the deep nuclei. This postmortem study links APOE epsilon4 to some vascular findings but does not show a treatment or prevention.
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Study details
- Evidence strengthLow
How this study scored 47/100
Published in a leading specialty 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 | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 1 / 5 | 2005 — older than 20 years, still counted |
| 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 155 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.7 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 3 / 6 | Cited 4.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 1 / 4 | Cited 11 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Lindsay A. Farrer: h-index 119 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Boston University: institution h-index 1,456 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16043796) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
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