Transthyretin binds amyloid β peptides, A β1–42 and A β1–40 to form complex in the autopsied human kidney – possible role of transthyretin for A β sequestration

• Published in: Neuroscience letters Vol. 281; no. 2; pp. 171 - 174
• Main Authors: Tsuzuki, Kayo, Fukatsu, Ryo, Yamaguchi, Haruyasu, Tateno, Masatoshi, Imai, Kohzoh, Fujii, Nobuhiro, Yamauchi, Toshio
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 10.03.2000; Elsevier
• Subjects: A β1–40; A β1–42; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Human kidney; Immunoprecipitation; Sequestration; Transthyretin; Vertebrates: urinary system; A β1–40; A β1–42; Human kidney; Immunoprecipitation; Transthyretin; Sequestration; Human; Binding; Urinary system; Thyroxine binding prealbumin; β Amyloid protein; Kidney
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(00)00834-X

The deposition of amyloid β protein (A β), 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 A β in the kidney, we have investigated interactions of TTR with A β1–40 and A β1–42 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 β1–42 preferentially, and A β1–40 only to a limited extent, to form TTR-monomer and -dimer-A β complexes in the normal human kidney. We provide new evidence supporting the hypothesis that TTR, an A β binding protein, plays an important role in the sequestration of A β and prevents amyloid formation in the kidney.