Cerebrovascular effects of apolipoprotein E: implications for Alzheimer disease
Zlokovic BV.. JAMA neurology, 2013-04-01
Topic: Amyloid, tau and blood-test diagnosis
Human apolipoprotein E (apoE) has 3 isoforms: apoE2, apoE3, and apoE4. APOE4 is a major genetic risk factor for Alzheimer disease and is associated with dementia in Down syndrome and poor neurological outcome after traumatic brain injury, cerebral hemorrhage, and other neuropathological disorders. While apoE4 can induce neuropathology by participating in various cellular and molecular pathways, herein I review data supporting the hypothesis that apoE4 has direct toxic effects on the cerebrovascular system that in turn can lead to secondary neuronal dysfunction and degeneration as well as accumulation of neurotoxins in brain such as β-amyloid (Aβ) in Alzheimer disease. I review Aβ-independent cerebrovascular effects of apoE, particularly activation of a proinflammatory cyclophilin A-mediated pathway in brain vascular pericytes by apoE4 that has recently been shown to lead to a loss of cerebrovascular integrity and blood-brain barrier breakdown causing neuronal injury. I also review Aβ-dependent cerebrovascular effects of apoE such as faulty Aβ clearance from brain to circulation by apoE4. Finally, I discuss isoform-specific interactions of apoE with low-density lipoprotein receptor-related protein 1 on brain vascular cells (ie, endothelial cells, pericytes), which play an important role in Aβ-independent and Aβ-dependent effects of apoE on cerebral vasculature.
Key findings
- APOE4 is a major genetic risk factor for Alzheimer disease and is associated with dementia in Down syndrome and poor neurological outcome after traumatic brain injury, cerebral hemorrhage, and other neuropathological disorders.
Why it matters
This review proposes that apoE4 has direct harmful effects on blood vessels in the brain, which could then lead to nerve cell damage and reduced clearance of amyloid. It is a hypothesis based on reviewed data and does not report any 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. We have no data on institution's track record, so that was left out: it earned 46 of the 97 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (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 | 2013 — within 20 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 263 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 17.5 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 4 / 6 | Cited 16.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 2 / 4 | Cited 37 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Berislav V. Zloković: h-index 118 (OpenAlex, whole career) |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 0 institution(s) in 0 countries — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23400708) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 46 / 97 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 46 of the 97 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamaneurol.2013.2152
- PubMed: 23400708
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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. Check the citation against the original before you use it.
APA 7th
Zlokovic, B. V. (2013). Cerebrovascular effects of apolipoprotein E: implications for Alzheimer disease. JAMA neurology. https://doi.org/10.1001/jamaneurol.2013.2152
Vancouver
Zlokovic BV. Cerebrovascular effects of apolipoprotein E: implications for Alzheimer disease. JAMA neurology. 2013. doi:10.1001/jamaneurol.2013.2152. PMID: 23400708.
BibTeX
@article{zlokovic2013-23400708,
author = {Zlokovic, B. V.},
title = {{Cerebrovascular effects of apolipoprotein E: implications for Alzheimer disease}},
journal = {JAMA neurology},
year = {2013},
doi = {10.1001/jamaneurol.2013.2152},
pmid = {23400708},
url = {https://doi.org/10.1001/jamaneurol.2013.2152}
}
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