Characterization of a sensitive mouse Aβ40 PD biomarker assay for Alzheimer's disease drug development in wild-type mice
| Autor: | Y. Joy Yu Zuchero, William H Montgomery, Laura DeForge, William J. Meilandt, Kwame Hoyte, Wilman Luk, Dongping He, Ryan J. Watts, Jasvinder K. Atwal, Kimberly Scearce-Levie, Yanmei Lu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Clinical Biochemistry Enzyme-Linked Immunosorbent Assay Mice Transgenic Endogeny Transferrin receptor Disease Analytical Chemistry Mice 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Antibodies Bispecific Drug Discovery Receptors Transferrin Amyloid precursor protein Animals Aspartic Acid Endopeptidases Humans Medicine General Pharmacology Toxicology and Pharmaceutics Amyloid beta-Peptides biology business.industry Brain General Medicine Peptide Fragments Disease Models Animal Medical Laboratory Technology 030104 developmental biology Drug development Immunology biology.protein Cancer research Biomarker (medicine) Amyloid Precursor Protein Secretases Antibody business Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Bioanalysis. 8:1067-1075 |
| ISSN: | 1757-6199 1757-6180 |
| DOI: | 10.4155/bio-2016-0003 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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