| Title |
Comparing the efficacy and neuroinflammatory potential of three anti-abeta antibodies
|
|---|---|
| Published in |
Acta Neuropathologica, October 2015
|
| DOI | 10.1007/s00401-015-1484-2 |
| Pubmed ID | |
| Authors |
James P. Fuller, Jeffrey B. Stavenhagen, Søren Christensen, Fredrik Kartberg, Martin J. Glennie, Jessica L. Teeling |
| Abstract |
Immunotherapy is a promising strategy for the treatment of Alzheimer's disease (AD). Antibodies directed against Amyloid Beta (Aβ) are able to successfully clear plaques and reverse cognitive deficits in mouse models. Excitement towards this approach has been tempered by high profile failures in the clinic, one key issue has been the development of inflammatory side effects in the brain (ARIAs). New antibodies are entering the clinic for Alzheimer's disease; therefore, it is important to learn all we can from the current generation. In this study, we directly compared 3 clinical candidates in the same pre-clinical model, with the same effector function, for their ability to clear plaques and induce inflammation in the brain. We produced murine versions of the antibodies: Bapineuzumab (3D6), Crenezumab (mC2) and Gantenerumab (chGantenerumab) with an IgG2a constant region. 18-month transgenic APP mice (Tg2576) were injected bilaterally into the hippocampus with 2 µg of each antibody or control. After 7 days, the mice tissue was analysed for clearance of plaques and neuroinflammation by histology and biochemical analysis. 3D6 was the best binder to plaques and in vitro, whilst mC2 bound the least strongly. This translated into 3D6 effectively clearing plaques and reducing the levels of insoluble Aβ, whilst chGantenerumab and mC2 did not. 3D6 caused a significant increase in the levels of pro-inflammatory cytokines IL-1β and TNFα, and an associated increase in microglial expression of CD11B and CD68. chGantenerumab increased pro-inflammatory cytokines and microglial activation, but minimal changes in CD68, as an indicator of phagocytosis. Injection of mC2 did not cause any significant inflammatory changes. Our results demonstrate that the ability of an antibody to clear plaques and induce inflammation is dependent on the epitope and affinity of the antibody. |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 33% |
| Unknown | 4 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 6 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 91 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Sweden | 1 | 1% |
| Germany | 1 | 1% |
| Unknown | 89 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 17 | 19% |
| Researcher | 16 | 18% |
| Student > Ph. D. Student | 10 | 11% |
| Other | 8 | 9% |
| Student > Doctoral Student | 7 | 8% |
| Other | 13 | 14% |
| Unknown | 20 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 17 | 19% |
| Biochemistry, Genetics and Molecular Biology | 14 | 15% |
| Neuroscience | 13 | 14% |
| Medicine and Dentistry | 7 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 4% |
| Other | 9 | 10% |
| Unknown | 27 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 61. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 October 2020.
All research outputs
#708,188
of 25,837,817 outputs
Outputs from Acta Neuropathologica
#97
of 2,606 outputs
Outputs of similar age
#10,174
of 291,770 outputs
Outputs of similar age from Acta Neuropathologica
#5
of 34 outputs
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So far Altmetric has tracked 2,606 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 17.3. This one has done particularly well, scoring higher than 94% of its peers.
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We're also able to compare this research output to 34 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 85% of its contemporaries.