| First Author | Wirths O | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 53 | Pages | 41517-24 |
| PubMed ID | 20971852 | Mgi Jnum | J:167567 |
| Mgi Id | MGI:4868550 | Doi | 10.1074/jbc.M110.178707 |
| Citation | Wirths O, et al. (2010) Identification of low molecular weight pyroglutamate A{beta} oligomers in Alzheimer disease: a novel tool for therapy and diagnosis. J Biol Chem 285(53):41517-24 |
| abstractText | N-terminally truncated Abeta peptides starting with pyroglutamate (AbetapE3) represent a major fraction of all Abeta peptides in the brain of Alzheimer disease (AD) patients. AbetapE3 has a higher aggregation propensity and stability and shows increased toxicity compared with full-length Abeta. In the present work, we generated a novel monoclonal antibody (9D5) that selectively recognizes oligomeric assemblies of AbetapE3 and studied the potential involvement of oligomeric AbetapE3 in vivo using transgenic mouse models as well as human brains from sporadic and familial AD cases. 9D5 showed an unusual staining pattern with almost nondetectable plaques in sporadic AD patients and non-demented controls. Interestingly, in sporadic and familial AD cases prominent intraneuronal and blood vessel staining was observed. Using a novel sandwich ELISA significantly decreased levels of oligomers in plasma samples from patients with AD compared with healthy controls were identified. Moreover, passive immunization of 5XFAD mice with 9D5 significantly reduced overall Abeta plaque load and AbetapE3 levels, and normalized behavioral deficits. These data indicate that 9D5 is a therapeutically and diagnostically effective monoclonal antibody targeting low molecular weight AbetapE3 oligomers. |
