PMID- 15312963 OWN - NLM STAT- MEDLINE DCOM- 20041221 LR - 20101118 IS - 0197-4580 (Print) IS - 0197-4580 (Linking) VI - 25 IP - 9 DP - 2004 Oct TI - Novel aspects of accumulation dynamics and A beta composition in transgenic models of AD. PG - 1175-85 AB - A homogeneous time-resolved fluorescence immunoassay for detection of beta-amyloid (A beta) peptides has been adapted for quantification of A beta(40) and A beta(42) accumulation in brains of APP695SWE transgenic mice. These over-express human beta APP(swe), beta-amyloid precursor protein (beta-APP) containing the K670N/M671L 'Swedish' familial Alzheimer's disease (FAD) mutation. Both peptides start to accumulate in this line from about 260 to 280 days of age. Co-expression of a human presenilin-1 (PS1) transgene containing the A246E FAD mutation accelerates deposition and also favors-at least initially-accumulation of A beta(42) so that the A beta(2):A beta(40) ratio of peptides from 7- to 12-month-old APP695SWE x PS1A246E animals is significantly elevated above that observed throughout the lifetime of APP695SWE mice. These findings, supported by parallel immunohistochemical staining and surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry data, offer important longitudinal characterization of two mouse models of cerebral amyloidosis. Application of the same extraction and quantitation procedures to samples of temporal cortex from AD sufferers indicates however that A beta(40) is only a minor component of beta-amyloid in humans. FAU - Lewis, Huw D AU - Lewis HD AD - Department of Molecular and Cellular Neuroscience, Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK. FAU - Beher, Dirk AU - Beher D FAU - Smith, David AU - Smith D FAU - Hewson, Louise AU - Hewson L FAU - Cookson, Natalie AU - Cookson N FAU - Reynolds, David S AU - Reynolds DS FAU - Dawson, Gerard R AU - Dawson GR FAU - Jiang, Michael AU - Jiang M FAU - Van der Ploeg, Lex H T AU - Van der Ploeg LH FAU - Qian, Su AU - Qian S FAU - Rosahl, Thomas W AU - Rosahl TW FAU - Kalaria, Raj N AU - Kalaria RN FAU - Shearman, Mark S AU - Shearman MS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Neurobiol Aging JT - Neurobiology of aging JID - 8100437 RN - 0 (Amyloid beta-Peptides) RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Membrane Proteins) RN - 0 (PSEN1 protein, human) RN - 0 (Peptide Fragments) RN - 0 (Presenilin-1) RN - 0 (amyloid beta-protein (1-40)) RN - 0 (amyloid beta-protein (1-42)) SB - IM MH - Aging/genetics/metabolism/pathology MH - Alzheimer Disease/genetics/*metabolism/physiopathology MH - Amyloid beta-Peptides/*analysis/genetics/metabolism MH - Amyloid beta-Protein Precursor/metabolism MH - Animals MH - Brain/*metabolism/pathology/physiopathology MH - Disease Models, Animal MH - Disease Progression MH - Fluorescence Polarization Immunoassay/methods MH - Gliosis/genetics/metabolism/physiopathology MH - Humans MH - Membrane Proteins/genetics/metabolism MH - Mice MH - Mice, Transgenic MH - Mutation/genetics MH - Peptide Fragments/analysis/genetics/metabolism MH - Plaque, Amyloid/chemistry/genetics/*metabolism MH - Presenilin-1 MH - Tumor Cells, Cultured MH - Up-Regulation/genetics EDAT- 2004/08/18 05:00 MHDA- 2004/12/22 09:00 CRDT- 2004/08/18 05:00 PHST- 2003/04/16 00:00 [received] PHST- 2003/10/20 00:00 [revised] PHST- 2003/12/11 00:00 [accepted] PHST- 2004/08/18 05:00 [pubmed] PHST- 2004/12/22 09:00 [medline] PHST- 2004/08/18 05:00 [entrez] AID - S0197458004000478 [pii] AID - 10.1016/j.neurobiolaging.2003.12.009 [doi] PST - ppublish SO - Neurobiol Aging. 2004 Oct;25(9):1175-85. doi: 10.1016/j.neurobiolaging.2003.12.009.