Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight
Shi Y, Holtzman DM.. Nature reviews. Immunology, 2018-12-01
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer disease is more than a pure proteopathy. Chronic neuroinflammation stands out during the pathogenesis of the disease and in turn modulates disease progression. The central nervous system (CNS) is separated from the blood circulation by the blood-brain barrier. In Alzheimer disease, neuroinflammation heavily relies on innate immune responses that are primarily mediated by CNS-resident microglia. APOE (which encodes apolipoprotein E) is the strongest genetic risk factor for Alzheimer disease, and APOE was recently shown to affect the disease in part through its immunomodulatory function. This function of APOE is likely linked to triggering receptor expressed on myeloid cells 2 (TREM2), which is expressed by microglia in the CNS. Here, we review the rapidly growing literature on the role of disease-associated microglia, TREM2 and APOE in the pathogenesis of Alzheimer disease and present an integrated view of innate immune function in Alzheimer disease.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Shi, Y., & Holtzman, D. M. (2018). Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight. Nature reviews. Immunology. https://doi.org/10.1038/s41577-018-0051-1
Vancouver
Shi Y, Holtzman DM. Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight. Nature reviews. Immunology. 2018. doi:10.1038/s41577-018-0051-1. PMID: 30140051.
BibTeX
@article{shi2018-30140051,
author = {Shi, Y. and Holtzman, D. M.},
title = {{Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight}},
journal = {Nature reviews. Immunology},
year = {2018},
doi = {10.1038/s41577-018-0051-1},
pmid = {30140051},
url = {https://doi.org/10.1038/s41577-018-0051-1}
}
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Key findings
- The central nervous system (CNS) is separated from the blood circulation by the blood-brain barrier.
- In Alzheimer disease, neuroinflammation heavily relies on innate immune responses that are primarily mediated by CNS-resident microglia.
- APOE (which encodes apolipoprotein E) is the strongest genetic risk factor for Alzheimer disease, and APOE was recently shown to affect the disease in part through its immunomodulatory function.
- This function of APOE is likely linked to triggering receptor expressed on myeloid cells 2 (TREM2), which is expressed by microglia in the CNS.
- Here, we review the rapidly growing literature on the role of disease-associated microglia, TREM2 and APOE in the pathogenesis of Alzheimer disease and present an integrated view of innate immune function in Alzheimer disease.
Why it matters
This 2018 review summarises earlier research and adds no new data. It describes APOE, which it calls "the strongest genetic risk factor for Alzheimer disease", as acting on the disease partly through the brain's innate immune system, where microglia drive most of the inflammation. It suggests this APOE effect is "likely linked" to TREM2, a receptor on microglia, but presents this as a hypothesis, and it reports no treatment, test or prevention.
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Study details
- Evidence strengthLow
How this study scored 54/100
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 (Nature reviews. Immunology) |
| Journal's citation record | 4 / 4 | Nature reviews. Immunology: journal h-index 570 (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 | 2018 — 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 | 6 / 7 | Cited 595 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 59.5 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 3 / 6 | Cited 5.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 38 other studies in this library |
| Still being cited | 3 / 4 | Cited 184 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author David M. Holtzman: h-index 206 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30140051) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 54 / 100 | — |
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