Accelerated A{beta} Deposition in APPswe/PS1 Delta E9 Mice with Hemizygous Deletions of TTR (Transthyretin)

A cardinal pathological lesion of Alzheimer's disease (AD) is the deposition of amyloid {szligbeta} (A{szligbeta}) in the brain. We previously reported that exposing transgenic mice harboring APPswe/PS1 Delta E9 transgenes to an enriched environment resulted in reduced levels of A{szligbeta} 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 A{szligbeta} peptides and modulate their aggregation in vitro and in vivo. To explore the impact of TTR expression on A{szligbeta} levels and deposition in vivo, we crossed ceAPPswe/PS1 Delta E9 transgenic mice to mice with genetic ablations of TTR. We now report that the levels of detergent-soluble and formic acid-soluble levels of A{szligbeta} and deposition are elevated in the brains of ceAPPswe/PS1 Delta E9/TTR+/- mice compared with age-matched ceAPPswe/PS1 Delta E9/TTR+/+ mice. Moreover, A{szligbeta} deposition is significantly accelerated in the hippocampus and cortex of ceAPPswe/PS1 Delta E9/TTR+/- mice. Our results strongly suggest that TTR plays a critical role in modulating A{szligbeta} deposition in vivo.