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Bioanalysis. 2016 May;8(10):1067-75. doi: 10.4155/bio-2016-0003. Epub 2016 Apr 20.

Characterization of a sensitive mouse Aβ40 PD biomarker assay for Alzheimer's disease drug development in wild-type mice.

Author information

1
Departments of Biochemical & Cellular Pharmacology & Neuroscience, Genentech, Inc., South San Francisco, CA, USA.
2
Departments of Neuroscience, Genentech, Inc., South San Francisco, CA, USA.

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 Aβ40 in mouse plasma, brain and CSF. In wild-type mice treated with a bispecific anti-TfR/BACE1 antibody, significant Aβ 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 Aβ40 assay enables the use of wild-type mice for preclinical PK/PD and efficacy studies of potential AD therapeutics.

KEYWORDS:

Alzheimer's disease; BACE1; ELISA; PD biomarker; mouse abeta; therapeutic antibody; transferrin receptor

PMID:
27094761
DOI:
10.4155/bio-2016-0003
[Indexed for MEDLINE]

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