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PMID: 14732699 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Increased soluble amyloid-beta peptide and memory deficits in amyloid model mice overexpressing the low-density lipoprotein receptor-related protein.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 4 ·2004-01-27 ·Pages 1075-80

Zerbinatti CV, Wozniak DF, Cirrito J, Cam JA, Osaka H, Bales KR, Zhuo M, Paul SM, Holtzman DM, Bu G

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.

MeSH Terms
Amyloid beta-Peptides/metabolism Animals Brain/metabolism Cells, Cultured Enzyme-Linked Immunosorbent Assay LDL-Receptor Related Proteins/metabolism Memory Disorders/metabolism Mice Mice, Inbred C3H Solubility
Chemicals
Amyloid beta-Peptides LDL-Receptor Related Proteins
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Zerbinatti Celina V
Departments of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA.
Wozniak David F
Cirrito John
Cam Judy A
Osaka Hiroshi
Bales Kelly R
Zhuo Min
Paul Steven M
Holtzman David M
Bu Guojun
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0305803101
Published
2004-01-27
Epub
2004-00-19
Pages
1075-80
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC327153
Subset
IM
Grants
NINDS NIH HHS · NS41872 · United States
NIA NIH HHS · P50 AG05681 · United States
NIA NIH HHS · P01 AG011355 · United States
NIA NIH HHS · P50 AG005681 · United States
NINDS NIH HHS · F32 NS041872 · United States
NIA NIH HHS · AG11355 · United States
External Links
PubMed source DOI: 10.1073/pnas.0305803101 PMC Full Text View journal details
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