Characterization of a sensitive mouse Aß40 PD biomarker assay for Alzheimer's disease drug development in wild-type mice.
Bioanalysis
; 8(10): 1067-75, 2016 May.
Article
em En
| MEDLINE
| ID: mdl-27094761
ABSTRACT
AIM:
Transgenic mice that overexpress human amyloid precursor protein with Swedish or London (APPswe or APPlon) mutations have been widely used for preclinical Alzheimer's disease (AD) drug development. AD patients, however, rarely possess these mutations or overexpress APP.RESULTS:
We developed a sensitive ELISA that specifically and accurately measures low levels of endogenous Aß40 in mouse plasma, brain and CSF. In wild-type mice treated with a bispecific anti-TfR/BACE1 antibody, significant Aß reductions were observed in the periphery and the brain. APPlon transgenic mice showed a slightly less reduction, whereas APPswe mice did not have any decrease.CONCLUSION:
This sensitive and well-characterized mouse Aß40 assay enables the use of wild-type mice for preclinical PK/PD and efficacy studies of potential AD therapeutics.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Peptídeos beta-Amiloides
/
Descoberta de Drogas
/
Doença de Alzheimer
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article