title: Interaction of human and mouse Abeta peptides.
abstract: Transgenic mice over-expressing mutant human amyloid precursor protein have become an important tool for research on Alzheimer's disease (AD) and, in particular, for therapeutic screening. Many models have reported formation of amyloid plaques with age as is detected in AD. However, the plaques generated in transgenic mice are more soluble than human plaques. Differences in solubility may occur for a number of reasons; one proposal is the presence of murine Abeta peptides within the CNS milieu. Here, we report the interaction of human and murine Abeta peptides, Abeta40 and Abeta42, utilizing a fluorescence assay to monitor formation of mixed pre-fibrillar aggregates, electron microscopy to examine morphological characteristics and detergent solubility to monitor stability. Our results demonstrate that interspecies Abeta aggregates and fibres are readily formed and are more stable than homogenous human fibres. Furthermore, these results suggest that the presence of endogenous murine Abeta in human APP transgenic mice does not account for the increased solubility of plaques.
authors.affiliation: Centre for Research in Neurodegenerative Diseases, Ontario Cancer Institute, Toronto, Ontario, Canada.
authors.forename: Justin
authors.initials: J
authors.lastname: Fung
authors.forename: David
authors.initials: D
authors.lastname: Frost
authors.forename: Avijit
authors.initials: A
authors.lastname: Chakrabartty
authors.forename: Joanne
authors.initials: J
authors.lastname: McLaurin
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000818:Animals; D004355:Drug Stability; D006801:Humans; D051379:Mice; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012995:Solubility; D013045:Species Specificity
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)