BRI2 (ITM2b) inhibits Aβ deposition in vivo

Jungsu Kim, Victor M. Miller, Yona Levites, Karen Jansen West, Craig W. Zwizinski, Brenda D. Moore, Fredrick J. Troendle, Maralyssa Bann, Christophe Verbeeck, Robert W. Price, Lisa Smithson, Leilani Sonoda, Kayleigh Wagg, Vijayaraghavan Rangachari, Fanggeng Zou, Steven G Younkin, Neill R Graff Radford, Dennis W Dickson, Terrone Rosenberry, Todd E. Golde

Research output: Contribution to journalArticle

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Abstract

Analyses of the biologic effects of mutations in the BRI2 (ITM2b) and the amyloid β precursor protein (APP) genes support the hypothesis that cerebral accumulation of amyloidogenic peptides in familial British and familial Danish dementias and Alzheimer's disease (AD) is associated with neurodegeneration. We have used somatic brain transgenic technology to express the BRI2 and BRI2-Aβ1-40 transgenes in APP mouse models. Expression of BRI2-Aβ1-40 mimics the suppressive effect previously observed using conventional transgenic methods, further validating the somatic brain transgenic methodology. Unexpectedly, we also find that expression of wild-type human BRI2 reduces cerebral Aβ deposition in an AD mouse model. Additional data indicate that the 23 aa peptide, Bri23, released from BRI2 by normal processing, is present in human CSF, inhibits Aβ aggregation in vitro and mediates its anti-amyloidogenic effect in vivo. These studies demonstrate that BRI2 is a novel mediator of Aβ deposition in vivo.

Original languageEnglish (US)
Pages (from-to)6030-6036
Number of pages7
JournalJournal of Neuroscience
Volume28
Issue number23
DOIs
StatePublished - Jun 4 2008

Fingerprint

Amyloid beta-Protein Precursor
Alzheimer Disease
Peptides
Brain
Transgenes
Technology
Mutation
Genes
In Vitro Techniques
Familial Danish dementia

Keywords

  • Adeno-associated virus
  • Alzheimer's disease
  • Amyloid β protein
  • BRI2
  • Itm2b
  • Somatic brain transgenesis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Kim, J., Miller, V. M., Levites, Y., West, K. J., Zwizinski, C. W., Moore, B. D., ... Golde, T. E. (2008). BRI2 (ITM2b) inhibits Aβ deposition in vivo. Journal of Neuroscience, 28(23), 6030-6036. https://doi.org/10.1523/JNEUROSCI.0891-08.2008

BRI2 (ITM2b) inhibits Aβ deposition in vivo. / Kim, Jungsu; Miller, Victor M.; Levites, Yona; West, Karen Jansen; Zwizinski, Craig W.; Moore, Brenda D.; Troendle, Fredrick J.; Bann, Maralyssa; Verbeeck, Christophe; Price, Robert W.; Smithson, Lisa; Sonoda, Leilani; Wagg, Kayleigh; Rangachari, Vijayaraghavan; Zou, Fanggeng; Younkin, Steven G; Graff Radford, Neill R; Dickson, Dennis W; Rosenberry, Terrone; Golde, Todd E.

In: Journal of Neuroscience, Vol. 28, No. 23, 04.06.2008, p. 6030-6036.

Research output: Contribution to journalArticle

Kim, J, Miller, VM, Levites, Y, West, KJ, Zwizinski, CW, Moore, BD, Troendle, FJ, Bann, M, Verbeeck, C, Price, RW, Smithson, L, Sonoda, L, Wagg, K, Rangachari, V, Zou, F, Younkin, SG, Graff Radford, NR, Dickson, DW, Rosenberry, T & Golde, TE 2008, 'BRI2 (ITM2b) inhibits Aβ deposition in vivo', Journal of Neuroscience, vol. 28, no. 23, pp. 6030-6036. https://doi.org/10.1523/JNEUROSCI.0891-08.2008
Kim J, Miller VM, Levites Y, West KJ, Zwizinski CW, Moore BD et al. BRI2 (ITM2b) inhibits Aβ deposition in vivo. Journal of Neuroscience. 2008 Jun 4;28(23):6030-6036. https://doi.org/10.1523/JNEUROSCI.0891-08.2008
Kim, Jungsu ; Miller, Victor M. ; Levites, Yona ; West, Karen Jansen ; Zwizinski, Craig W. ; Moore, Brenda D. ; Troendle, Fredrick J. ; Bann, Maralyssa ; Verbeeck, Christophe ; Price, Robert W. ; Smithson, Lisa ; Sonoda, Leilani ; Wagg, Kayleigh ; Rangachari, Vijayaraghavan ; Zou, Fanggeng ; Younkin, Steven G ; Graff Radford, Neill R ; Dickson, Dennis W ; Rosenberry, Terrone ; Golde, Todd E. / BRI2 (ITM2b) inhibits Aβ deposition in vivo. In: Journal of Neuroscience. 2008 ; Vol. 28, No. 23. pp. 6030-6036.
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