title: Increased soluble amyloid-beta peptide and memory deficits in amyloid model mice overexpressing the low-density lipoprotein receptor-related protein.
abstract: Amyloid-beta peptide (Abeta) is central to the pathogenesis of Alzheimer's disease, and the low-density lipoprotein receptor-related protein (LRP) has been shown to alter Abeta metabolism in vitro. Here, we show that overexpression of a functional LRP minireceptor in the brain of PDAPP mice results in age-dependent increase of soluble brain Abeta, with no changes in Abeta plaque burden. Importantly, soluble brain Abeta was found to be primarily in the form of monomers/dimers and to be highly correlated with deficits in spatial learning and memory. These results provide in vivo evidence that LRP may contribute to memory deficits typical of Alzheimer's disease by modulating the pool of small soluble forms of Abeta.
authors.affiliation: Departments of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Celina V
authors.initials: CV
authors.lastname: Zerbinatti
authors.forename: David F
authors.initials: DF
authors.lastname: Wozniak
authors.forename: John
authors.initials: J
authors.lastname: Cirrito
authors.forename: Judy A
authors.initials: JA
authors.lastname: Cam
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Osaka
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Bales
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
authors.forename: Steven M
authors.initials: SM
authors.lastname: Paul
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
authors.forename: Guojun
authors.initials: G
authors.lastname: Bu
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D026502:LDL-Receptor Related Proteins / Q000378:metabolism*; D008569:Memory Disorders / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D012995:Solubility
chemical_list: D016229:Amyloid beta-Peptides; D026502:LDL-Receptor Related Proteins