| First Author | Colvin BA | Year | 2017 |
| Journal | J Neurochem | Volume | 143 |
| Issue | 6 | Pages | 736-749 |
| PubMed ID | 28881033 | Mgi Jnum | J:336389 |
| Mgi Id | MGI:6102491 | Doi | 10.1111/jnc.14211 |
| Citation | Colvin BA, et al. (2017) The conformational epitope for a new Abeta42 protofibril-selective antibody partially overlaps with the peptide N-terminal region. J Neurochem 143(6):736-749 |
| abstractText | Aggregation and accumulation of amyloid-beta peptide (Abeta) is a key component of Alzheimer''s disease (AD). While monomeric Abeta appears to be benign, oligomers adopt a biologically detrimental structure. These soluble structures can be detected in AD brain tissue by antibodies that demonstrate selectivity for aggregated Abeta. Protofibrils are a subset of soluble oligomeric Abeta species and are described as small (< 100 nm) curvilinear assemblies enriched in beta-sheet structure. Our own in vitro studies demonstrate that microglial cells are much more sensitive to soluble Abeta42 protofibrils compared to Abeta42 monomer or insoluble Abeta42 fibrils. Protofibrils interact with microglia, trigger Toll-like receptor signaling, elicit cytokine transcription and expression, and are rapidly taken up by the cells. Because of the importance of this Abeta species, we sought to develop an antibody that selectively recognizes protofibrils over other Abeta species. Immunization of rabbits with isolated Abeta42 protofibrils generated a high-titer anti serum with a strong affinity for Abeta42 protofibrils. The antiserum, termed AbSL, was selective for Abeta42 protofibrils over Abeta42 monomers and Abeta42 fibrils. AbSL did not react with amyloid precursor protein and recognized distinct pathological features in AD transgenic mouse brain slices. Competition studies with an Abeta antibody that targets residues 1-16 indicated that the conformational epitope for AbSL involved the N-terminal region of protofibrils in some manner. The newly developed antibody may have potential diagnostic and therapeutic uses in AD tissue and patients, and targeting of protofibrils in AD may have beneficial effects. Read the Editorial Highlight for this article on page 621. Cover Image for this issue: doi. 10.1111/jnc.13827. |
