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Inflammation in Alzheimer’s disease: insights from immunotherapy
Jonathan M. Schott, Tamás Révész. Brain, 2013-08-26
Topic: Inflammation, microglia and astrocytes
Genome-wide association studies have identified a number of risk variants for Alzheimer’s disease implicated in inflammatory responses (Bettens et al., 2013); exome sequencing has revealed polymorphisms in the microglial receptor TREM2 gene as a rare but significant risk for Alzheimer’s disease (Guerreiro et al., 2013; Jonsson et al., 2013); and recently, the CD33 risk allele has been shown to inhibit microglial clearance of amyloid-β (Bradshaw et al., 2013; Griciuc et al., 2013). The first such study in man (AN1792) was halted after 6% of those on active therapy developed significant brain inflammation (Gilman et al., 2005). Aside from the meningoencephalitis that complicated the original AN1792 trial (Fox et al., 2005), in several studies, and particularly in ApoE ε4 carriers, immunotherapy has been associated with ‘amyloid-related imaging abnormalities’—often asymptomatic and usually mild and reversible oedema/effusions (ARIA-E) or haemosiderin deposition (ARIA-H), that may reflect immune-related flux of amyloid pathology in/out of vessels (Sperling et al., 2011). Finally, significant reduction in brain amyloid-β pathology has been demonstrated in the few treated patients that have thus far come to post-mortem (Holmes et al., 2008). Despite the significant progress that has been made in identifying inflammation as a core feature of Alzheimer’s disease, many fundamental questions remain. Those vaccinated against amyloid-β had substantial (82%) reductions in fibrillar amyloid-β42 load compared with those who did not receive treatment, demonstrating that, as previously reported (Holmes et al., 2008), peripheral vaccination against amyloid-β has clear and significant effects on its primary target within the brain. Treated individuals also showed significant (40%) reduction in phosphorylated tau burden in neuronal cell processes [although not in neurofibrillary tangles (Boche et al., 2010)], suggesting that in some way immune targeting of amyloid-β pathology has effects on other, likely downstream, pathologies involved in Alzheimer’s disease pathogenesis. Although there was no difference in total microglial load, vaccinated individuals showed significantly reduced levels of a range of activated microglial species, including those involved in innate immunity and antibody-mediated amyloid-β removal, suggesting a general downregulation of inflammation despite, on average, several years elapsing between vaccination and death. Taken together, these observations p
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Schott, J. M., & Révész, T. (2013). Inflammation in Alzheimer’s disease: insights from immunotherapy. Brain. https://doi.org/10.1093/brain/awt231
Vancouver
Schott JM, Révész T. Inflammation in Alzheimer’s disease: insights from immunotherapy. Brain. 2013. doi:10.1093/brain/awt231. PMID: 23983027.
BibTeX
@article{schott2013-23983027,
author = {Schott, Jonathan M. and Révész, Tamás},
title = {{Inflammation in Alzheimer’s disease: insights from immunotherapy}},
journal = {Brain},
year = {2013},
doi = {10.1093/brain/awt231},
pmid = {23983027},
url = {https://doi.org/10.1093/brain/awt231}
}
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
- Genome-wide association studies have identified a number of risk variants for Alzheimer’s disease implicated in inflammatory responses (Bettens et al., 2013); exome sequencing has revealed polymorphisms in the microglial receptor TREM2 gene as a rare but significant risk for Alzheimer’s disease (Guerreiro et al., 2013; Jonsson et al., 2013); and recently, the CD33 risk allele has been shown to inhibit microglial clearance of amyloid-β (Bradshaw et al., 2013; Griciuc et al., 2013).
- The first such study in man (AN1792) was halted after 6% of those on active therapy developed significant brain inflammation (Gilman et al., 2005).
- Aside from the meningoencephalitis that complicated the original AN1792 trial (Fox et al., 2005), in several studies, and particularly in ApoE ε4 carriers, immunotherapy has been associated with ‘amyloid-related imaging abnormalities’—often asymptomatic and usually mild and reversible oedema/effusions (ARIA-E) or haemosiderin deposition (ARIA-H), that may reflect immune-related flux of amyloid pathology in/out of vessels (Sperling et al., 2011).
- Finally, significant reduction in brain amyloid-β pathology has been demonstrated in the few treated patients that have thus far come to post-mortem (Holmes et al., 2008).
- Despite the significant progress that has been made in identifying inflammation as a core feature of Alzheimer’s disease, many fundamental questions remain.
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Study details
- Participants39
- Evidence strengthLow
How this study scored 47/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 1 / 4 | 39 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23983027) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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