Transthyretin binds amyloid beta peptides, A beta 1-42 and A beta 1-40 to form complex in the autopsied human kidney - possible role of transthyretinfor A beta sequestration

The deposition of amyloid beta protein (A beta), a proteolytic cleavage pro duct of amyloid precursor protein (APP), is an invariable pathological feat ure of the Alzheimer's disease brain, while APP gene is widely expressed in all neuronal and non-neuronal tissues with the highest levels of expressio n in the brain, and kidney. To understand the role transthyretin (TTR) play s 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 immuno precipitation method, in vitro binding studies, and overlay assay. These in vivo and in vitro biochemical experiments showed that TTR bound A beta 1-4 2 preferentially, and A beta 1-40 only to a limited extent, to form TTR-mon omer and -dimer-A beta complexes in the normal human kidney. We provide new evidence supporting the hypothesis that TTR, an A beta binding protein, pl ays an important role in the sequestration of A beta and prevents amyloid f ormation in the kidney. (C) 2000 Elsevier Science Ireland Ltd. All rights r eserved.