Accelerated Abeta deposition in APPswe/PS1deltaE9 mice with hemizygous deletions of TTR (transthyretin).
A cardinal pathological lesion of Alzheimer's disease (AD) is the deposition of amyloid beta (Abeta) in the brain. We previously reported that exposing transgenic mice harboring APPswe/PS1deltaE9 transgenes to an enriched environment resulted in reduced levels of Abeta 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 Abeta peptides and modulate their aggregation in vitro and in vivo. To explore the impact of TTR expression on Abeta levels and deposition in vivo, we crossed ceAPPswe/PS1deltaE9 transgenic mice to mice with genetic ablations of TTR. We now report that the levels of detergent-soluble and formic acid-soluble levels of Abeta and deposition are elevated in the brains of ceAPPswe/PS1deltaE9/TTR+/- mice compared with age-matched ceAPPswe/PS1deltaE9/TTR+/+ mice. Moreover, Abeta deposition is significantly accelerated in the hippocampus and cortex of ceAPPswe/PS1deltaE9/TTR+/- mice. Our results strongly suggest that TTR plays a critical role in modulating Abeta deposition in vivo.
Choi
Se Hoon
SH
Committee on Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.
Leight
Susan N
SN
Lee
Virginia M-Y
VM
Li
Tong
T
Wong
Philip C
PC
Johnson
Jeffrey A
JA
Saraiva
Maria J
MJ
Sisodia
Sangram S
SS
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism; D011228:Prealbumin / Q000235:genetics*; D053764:Presenilin-1 / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D011228:Prealbumin; D053764:Presenilin-1