JCB logo
CrossRef
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 10 January 2005. doi:10.1083/jcb.200407070
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 168, Number 2, 291-302
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 4060K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lee, E. B.
Right arrow Articles by Lee, V. M.-Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, E. B.
Right arrow Articles by Lee, V. M.-Y.
Right arrowPubmed/NCBI databases
*OMIM
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Article

BACE overexpression alters the subcellular processing of APP and inhibits Aß deposition in vivo



Edward B. Lee1, Bin Zhang1, Kangning Liu1, Eric A. Greenbaum1, Robert W. Doms2, John Q. Trojanowski1,3, and Virginia M.-Y. Lee1,3

1 The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine
2 Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
3 Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA 19104

Correspondence to Virginia M.-Y. Lee: vmylee{at}mail.med.upenn.edu

Introducing mutations within the amyloid precursor protein (APP) that affect ß- and {gamma}-secretase cleavages results in amyloid plaque formation in vivo. However, the relationship between ß-amyloid deposition and the subcellular site of Aß production is unknown. To determine the effect of increasing ß-secretase (BACE) activity on Aß deposition, we generated transgenic mice overexpressing human BACE. Although modest overexpression enhanced amyloid deposition, high BACE overexpression inhibited amyloid formation despite increased ß-cleavage of APP. However, high BACE expression shifted the subcellular location of APP cleavage to the neuronal perikarya early in the secretory pathway. These results suggest that the production, clearance, and aggregation of Aß peptides are highly dependent on the specific neuronal subcellular domain wherein Aß is generated and highlight the importance of perikaryal versus axonal APP proteolysis in the development of Aß amyloid pathology in Alzheimer's disease.

Abbreviations used in this paper: AD, Alzheimer's disease; APP, amyloid precursor protein; BACE, ß-secretase; FA, formic acid; IDE, insulin-degrading enzyme; NFM, molecular weight neurofilament subunit; PhAT, anti–phospho-APP-threonine 668; PrP, prion protein; Tg, transgenic.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents