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Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?
Leng F, Edison P.. Nature reviews. Neurology, 2020-12-14
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer disease (AD) is the most common form of neurodegenerative disease, estimated to contribute 60-70% of all cases of dementia worldwide. According to the prevailing amyloid cascade hypothesis, amyloid-β (Aβ) deposition in the brain is the initiating event in AD, although evidence is accumulating that this hypothesis is insufficient to explain many aspects of AD pathogenesis. The discovery of increased levels of inflammatory markers in patients with AD and the identification of AD risk genes associated with innate immune functions suggest that neuroinflammation has a prominent role in the pathogenesis of AD.
Key findings
- According to the prevailing amyloid cascade hypothesis, amyloid-β (Aβ) deposition in the brain is the initiating event in AD, although evidence is accumulating that this hypothesis is insufficient to explain many aspects of AD pathogenesis.
- The discovery of increased levels of inflammatory markers in patients with AD and the identification of AD risk genes associated with innate immune functions suggest that neuroinflammation has a prominent role in the pathogenesis of AD.
- In this Review, we discuss the interrelationships between neuroinflammation and amyloid and tau pathologies as well as the effect of neuroinflammation on the disease trajectory in AD.
- We specifically focus on microglia as major players in neuroinflammation and discuss the spatial and temporal variations in microglial phenotypes that are observed under different conditions.
Why it matters
This 2021 review argues that the amyloid cascade hypothesis, which holds that amyloid-β build-up in the brain is the starting event, is "insufficient to explain many aspects" of Alzheimer's. It says raised inflammatory markers in patients and risk genes tied to innate immunity "suggest" that brain inflammation plays a prominent role, and it looks at how inflammation interacts with amyloid and tau, focusing on microglia, the brain's immune cells. It is a review of existing evidence, not a new study, and reports no treatment, cure or prevention.
Study details
- Evidence strengthLow
How this study scored 57/100
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. Neurology) |
| Journal's citation record | 3 / 4 | Nature Reviews Neurology: journal h-index 269 (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 | 3 / 5 | 2021 — within 6 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 | 7 / 7 | Cited 3,143 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 449.0 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 5 / 6 | Cited 36.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 73 other studies in this library |
| Still being cited | 4 / 4 | Cited 1,970 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Paul Edison: h-index 53 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Imperial College London: institution h-index 1,744 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33318676) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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
Leng, F., & Edison, P. (2021). Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nature reviews. Neurology. https://doi.org/10.1038/s41582-020-00435-y
Vancouver
Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nature reviews. Neurology. 2021. doi:10.1038/s41582-020-00435-y. PMID: 33318676.
BibTeX
@article{leng2021-33318676,
author = {Leng, F. and Edison, P.},
title = {{Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?}},
journal = {Nature reviews. Neurology},
year = {2021},
doi = {10.1038/s41582-020-00435-y},
pmid = {33318676},
url = {https://doi.org/10.1038/s41582-020-00435-y}
}
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