Cell type-specific roles of APOE4 in Alzheimer disease
Blumenfeld J, Yip O, Kim MJ, Huang Y.. Nature reviews. Neuroscience, 2024-01-08
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
The ɛ4 allele of the apolipoprotein E gene (APOE), which translates to the APOE4 isoform, is the strongest genetic risk factor for late-onset Alzheimer disease (AD). Within the CNS, APOE is produced by a variety of cell types under different conditions, posing a challenge for studying its roles in AD pathogenesis. However, through powerful advances in research tools and the use of novel cell culture and animal models, researchers have recently begun to study the roles of APOE4 in AD in a cell type-specific manner and at a deeper and more mechanistic level than ever before. In particular, cutting-edge omics studies have enabled APOE4 to be studied at the single-cell level and have allowed the identification of critical APOE4 effects in AD-vulnerable cellular subtypes. Through these studies, it has become evident that APOE4 produced in various types of CNS cell - including astrocytes, neurons, microglia, oligodendrocytes and vascular cells - has diverse roles in AD pathogenesis. Here, we review these scientific advances and propose a cell type-specific APOE4 cascade model of AD. In this model, neuronal APOE4 emerges as a crucial pathological initiator and driver of AD pathogenesis, instigating glial responses and, ultimately, neurodegeneration. In addition, we provide perspectives on future directions for APOE4 research and related therapeutic developments in the context of AD.
What this study adds
Evidence grade: Low
This is a narrative review. This review describes how the APOE4 risk gene acts differently in different brain cell types, with APOE4 in neurons proposed as an early driver of the disease process. It is a summary of research and a proposed model, not a treatment or cure, though it points to possible future therapeutic directions.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Blumenfeld, J., Yip, O., Kim, M. J., & Huang, Y. (2024). Cell type-specific roles of APOE4 in Alzheimer disease. Nature reviews. Neuroscience. https://doi.org/10.1038/s41583-023-00776-9
Vancouver
Blumenfeld J, Yip O, Kim MJ, Huang Y. Cell type-specific roles of APOE4 in Alzheimer disease. Nature reviews. Neuroscience. 2024. doi:10.1038/s41583-023-00776-9. PMID: 38191720.
BibTeX
@article{blumenfeld2024-38191720,
author = {Blumenfeld, J. and Yip, O. and Kim, M. J. and Huang, Y.},
title = {{Cell type-specific roles of APOE4 in Alzheimer disease}},
journal = {Nature reviews. Neuroscience},
year = {2024},
doi = {10.1038/s41583-023-00776-9},
pmid = {38191720},
url = {https://doi.org/10.1038/s41583-023-00776-9}
}
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.
Key findings
- In particular, cutting-edge omics studies have enabled APOE4 to be studied at the single-cell level and have allowed the identification of critical APOE4 effects in AD-vulnerable cellular subtypes.
- Through these studies, it has become evident that APOE4 produced in various types of CNS cell - including astrocytes, neurons, microglia, oligodendrocytes and vascular cells - has diverse roles in AD pathogenesis.
- Here, we review these scientific advances and propose a cell type-specific APOE4 cascade model of AD.
- In this model, neuronal APOE4 emerges as a crucial pathological initiator and driver of AD pathogenesis, instigating glial responses and, ultimately, neurodegeneration.
- In addition, we provide perspectives on future directions for APOE4 research and related therapeutic developments in the context of AD.
Why it matters
This review describes how the APOE4 risk gene acts differently in different brain cell types, with APOE4 in neurons proposed as an early driver of the disease process. It is a summary of research and a proposed model, not a treatment or cure, though it points to possible future therapeutic directions.
New to this subject? Start with our plain-English guide: Genetics →
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 randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Nature reviews. Neuroscience) |
| Journal's citation record | 4 / 4 | Nature reviews. Neuroscience: journal h-index 572 (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 | 4 / 5 | 2024 — within 3 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 191 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 47.8 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 4 / 6 | Cited 14.7× 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 191 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Yadong Huang: h-index 73 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38191720) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
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