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The Journal of Neuroscience, June 27, 2007, 27(26):7006-7010; doi:10.1523/JNEUROSCI.1919-07.2007

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Brief Communications
Accelerated Aß Deposition in APPswe/PS1E9 Mice with Hemizygous Deletions of TTR (Transthyretin)

Se Hoon Choi,¹ Susan N. Leight,³ Virginia M.-Y. Lee,³ Tong Li,⁴ Philip C. Wong,⁴ Jeffrey A. Johnson,⁵ Maria J. Saraiva,⁶ and Sangram S. Sisodia²

¹Committee on Neurobiology and ²Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, ³Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, ⁴Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, ⁵Neuroscience Training Program, University of Wisconsin, Madison, Wisconsin 53705, and ⁶Institute of Molecular and Cellular Biology, Porto, Portugal

Correspondence should be addressed to Sangram S. Sisodia, Department of Neurobiology, The University of Chicago, 947 East 58th Street, AB 308, Chicago, IL 60637. Email: ssisodia{at}bsd.uchicago.edu

A cardinal pathological lesion of Alzheimer's disease (AD) is the deposition of amyloid ß (Aß) in the brain. We previously reported that exposing transgenic mice harboring APPswe/PS1E9 transgenes to an enriched environment resulted in reduced levels of Aß peptides and deposition, findings that were correlated with an increase in the expression of TTR, encoding transthyretin (TTR). TTR is expressed at high levels in the choroid plexus and known to bind Aß peptides and modulate their aggregation in vitro and in vivo. To explore the impact of TTR expression on Aß levels and deposition in vivo, we crossed ceAPPswe/PS1E9 transgenic mice to mice with genetic ablations of TTR. We now report that the levels of detergent-soluble and formic acid-soluble levels of Aß and deposition are elevated in the brains of ceAPPswe/PS1E9/TTR+/– mice compared with age-matched ceAPPswe/PS1E9/TTR+/+ mice. Moreover, Aß deposition is significantly accelerated in the hippocampus and cortex of ceAPPswe/PS1E9/TTR+/– mice. Our results strongly suggest that TTR plays a critical role in modulating Aß deposition in vivo.

Key words: transthyretin; presenilin 1; transgenic mice; Aß peptide; Alzheimer's disease; amyloid

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Received April 27, 2007; accepted May 18, 2007.

Correspondence should be addressed to Sangram S. Sisodia, Department of Neurobiology, The University of Chicago, 947 East 58th Street, AB 308, Chicago, IL 60637. Email: ssisodia{at}bsd.uchicago.edu

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				L. Liu, J. Hou, J. Du, R. S. Chumanov, Q. Xu, Y. Ge, J. A. Johnson, and R. M. Murphy Differential modification of Cys10 alters transthyretin's effect on beta-amyloid aggregation and toxicity Protein Eng. Des. Sel., August 1, 2009; 22(8): 479 - 488. [Abstract] [Full Text] [PDF]

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