PMID- 12558980 OWN - NLM STAT- MEDLINE DCOM- 20030214 LR - 20190630 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 84 IP - 3 DP - 2003 Feb TI - Characterization of amyloid beta peptides from brain extracts of transgenic mice overexpressing the London mutant of human amyloid precursor protein. PG - 602-9 AB - Alzheimer's disease (AD) is marked by the presence of neurofibrillary tangles and amyloid plaques in the brain of patients. To study plaque formation, we report on further quantitative and qualitative analysis of human and mouse amyloid beta peptides (Abeta) from brain extracts of transgenic mice overexpressing the London mutant of human amyloid precursor protein (APP). Using enzyme-linked immunosorbant assays (ELISAs) specific for either human or rodent Abeta, we found that the peptides from both species aggregated to form plaques. The ratios of deposited Abeta1-42/1-40 were in the order of 2-3 for human and 8-9 for mouse peptides, indicating preferential deposition of Abeta42. We also determined the identity and relative levels of other Abeta variants present in protein extracts from soluble and insoluble brain fractions. This was done by combined immunoprecipitation and mass spectrometry (IP/MS). The most prominent peptides truncated either at the carboxyl- or the amino-terminus were Abeta1-38 and Abeta11-42, respectively, and the latter was strongly enriched in the extracts of deposited peptides. Taken together, our data indicate that plaques of APP-London transgenic mice consist of aggregates of multiple human and mouse Abeta variants, and the human variants that we identified were previously detected in brain extracts of AD patients. FAU - Pype, Stefan AU - Pype S AD - Johnson & Johnson Pharmaceutical Research & Development, a division of Janssen Pharmaceutica, Turnhoutseweg, Beerse, Belgium. FAU - Moechars, Dieder AU - Moechars D FAU - Dillen, Lieve AU - Dillen L FAU - Mercken, Marc AU - Mercken M LA - eng PT - Journal Article PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Amyloid beta-Peptides) RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Peptide Fragments) RN - 0 (Tissue Extracts) RN - 0 (amyloid beta-protein (1-40)) RN - 0 (amyloid beta-protein (1-42)) SB - IM MH - Alzheimer Disease/genetics MH - Amino Acid Sequence MH - Amyloid beta-Peptides/biosynthesis/*chemistry/*metabolism MH - Amyloid beta-Protein Precursor/genetics/*metabolism MH - Animals MH - Brain/metabolism/pathology MH - Brain Chemistry MH - Disease Models, Animal MH - Female MH - Humans MH - Male MH - Mice MH - Mice, Transgenic MH - Molecular Sequence Data MH - Mutation MH - Peptide Fragments/biosynthesis/*chemistry MH - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization MH - Tissue Extracts/*chemistry EDAT- 2003/02/01 04:00 MHDA- 2003/02/15 04:00 CRDT- 2003/02/01 04:00 PHST- 2003/02/01 04:00 [pubmed] PHST- 2003/02/15 04:00 [medline] PHST- 2003/02/01 04:00 [entrez] AID - 1556 [pii] AID - 10.1046/j.1471-4159.2003.01556.x [doi] PST - ppublish SO - J Neurochem. 2003 Feb;84(3):602-9. doi: 10.1046/j.1471-4159.2003.01556.x.