期刊
BIOANALYSIS
卷 8, 期 10, 页码 1067-1075出版社
FUTURE SCI LTD
DOI: 10.4155/bio-2016-0003
关键词
Alzheimer's disease; BACE1; ELISA; mouse abeta; PD biomarker; therapeutic antibody; transferrin receptor
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 A beta 40 in mouse plasma, brain and CSF. In wild-type mice treated with a bispecific anti-TfR/BACE1 antibody, significant A beta 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 A beta 40 assay enables the use of wild-type mice for preclinical PK/PD and efficacy studies of potential AD therapeutics.
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