Transthyretin binds amyloid β peptides, Aβ1-42 and Aβ1-40 to form complex in the autopsied human kidney -: possible role of transthyretin for Aβ sequestration

The deposition of amyloid beta protein (A beta), a proteolytic cleavage product of amyloid precursor protein (APP), is an invariable pathological feature of the Alzheimer's disease brain, while APP gene is widely expressed in all neuronal and non-neuronal tissues with the highest levels of expression in the brain, and kidney. To understand the role transthyretin (TTR) plays in the sequestration mechanism of AP in the kidney, we have investigated interactions of TTR with A beta 1-40 and A beta 1-42 molecules by an immunoprecipitation method, in vitro binding studies, and overlay assay. These in vivo and in vitro biochemical experiments showed that TTR bound A beta 1-42 preferentially, and A beta 1-40 only to a limited extent, to form TTR-monomer and -dimer-A beta complexes in the normal human kidney. We provide new evidence supporting the hypothesis that TTR, an A beta binding protein, plays an important role in the sequestration of A beta and prevents amyloid formation in the kidney. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.