Transgenic expression of ß1 antibody in brain neurons impairs age-dependent amyloid deposition in APP23 mice.
Neurobiol Aging
; 34(12): 2866-78, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-23870837
ABSTRACT
Heterologous expression of the functional amyloid beta (Aß) antibody ß1 in the central nervous system was engineered to maximize antibody exposure in the brain and assess the effects on Aß production and accumulation in these conditions. A single open reading frame encoding the heavy and light chains of ß1 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 ß1 administration were obtained. Similar brain and plasma ß1 concentrations indicated robust antibody efflux from the brain. In preplaque mice, ß1 formed a complex with Aß that caused a modest Aß increase in brain and plasma. At 11 months of age, ß1 expression reduced amyloid by 97% compared with age-matched APP23 mice. Interference of ß1 with ß-secretase cleavage of amyloid precursor protein was relatively small. Our data suggest that severely impaired amyloid formation was primarily mediated by a complex of ß1 with soluble Aß, which might have prevented Aß aggregation or favored transport out of the brain.
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MEDLINE
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Encéfalo
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Peptídeos beta-Amiloides
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Doença de Alzheimer
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Imunoterapia
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Animals
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En
Revista:
Neurobiol Aging
Ano de publicação:
2013
Tipo de documento:
Article