Increased soluble amyloid-beta peptide and memory deficits in amyloid model mice overexpressing the low-density lipoprotein receptor-related protein.
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.
Zerbinatti
Celina V
CV
Departments of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA.
Wozniak
David F
DF
Cirrito
John
J
Cam
Judy A
JA
Osaka
Hiroshi
H
Bales
Kelly R
KR
Zhuo
Min
M
Paul
Steven M
SM
Holtzman
David M
DM
Bu
Guojun
G
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
D016229:Amyloid beta-Peptides; D026502:LDL-Receptor Related Proteins