| First Author | Paganetti P | Year | 2013 |
| Journal | Neurobiol Aging | Volume | 34 |
| Issue | 12 | Pages | 2866-78 |
| PubMed ID | 23870837 | Mgi Jnum | J:211718 |
| Mgi Id | MGI:5576084 | Doi | 10.1016/j.neurobiolaging.2013.06.013 |
| Citation | Paganetti P, et al. (2013) Transgenic expression of beta1 antibody in brain neurons impairs age-dependent amyloid deposition in APP23 mice. Neurobiol Aging 34(12):2866-78 |
| abstractText | Heterologous expression of the functional amyloid beta (Abeta) antibody beta1 in the central nervous system was engineered to maximize antibody exposure in the brain and assess the effects on Abeta production and accumulation in these conditions. A single open reading frame encoding the heavy and light chains of beta1 linked by the mouth and foot virus peptide 2A was expressed in brain neurons of transgenic mice. Two of the resulting BIN66 transgenic lines were crossed with APP23 mice, which develop severe central amyloidosis. Brain concentrations at steady-state 5 times greater than those found after peripheral beta1 administration were obtained. Similar brain and plasma beta1 concentrations indicated robust antibody efflux from the brain. In preplaque mice, beta1 formed a complex with Abeta that caused a modest Abeta increase in brain and plasma. At 11 months of age, beta1 expression reduced amyloid by 97% compared with age-matched APP23 mice. Interference of beta1 with beta-secretase cleavage of amyloid precursor protein was relatively small. Our data suggest that severely impaired amyloid formation was primarily mediated by a complex of beta1 with soluble Abeta, which might have prevented Abeta aggregation or favored transport out of the brain. |
