TY - JOUR
T1 - BRI2 (ITM2b) inhibits Aβ deposition in vivo
AU - Kim, Jungsu
AU - Miller, Victor M.
AU - Levites, Yona
AU - West, Karen Jansen
AU - Zwizinski, Craig W.
AU - Moore, Brenda D.
AU - Troendle, Fredrick J.
AU - Bann, Maralyssa
AU - Verbeeck, Christophe
AU - Price, Robert W.
AU - Smithson, Lisa
AU - Sonoda, Leilani
AU - Wagg, Kayleigh
AU - Rangachari, Vijayaraghavan
AU - Zou, Fanggeng
AU - Younkin, Steven G.
AU - Graff-Radford, Neill
AU - Dickson, Dennis
AU - Rosenberry, Terrone
AU - Golde, Todd E.
PY - 2008/6/4
Y1 - 2008/6/4
N2 - 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.
AB - 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.
KW - Adeno-associated virus
KW - Alzheimer's disease
KW - Amyloid β protein
KW - BRI2
KW - Itm2b
KW - Somatic brain transgenesis
UR - http://www.scopus.com/inward/record.url?scp=44949217679&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44949217679&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0891-08.2008
DO - 10.1523/JNEUROSCI.0891-08.2008
M3 - Article
C2 - 18524908
AN - SCOPUS:44949217679
SN - 0270-6474
VL - 28
SP - 6030
EP - 6036
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 23
ER -