title: Transthyretin sequesters amyloid beta protein and prevents amyloid formation.
abstract: The cardinal pathological features of Alzheimer disease are depositions of aggregated amyloid beta protein (A beta) in the brain and cerebrovasculature. However, the A beta is found in a soluble form in cerebrospinal fluid in healthy individuals and patients with Alzheimer disease. We postulate that sequestration of A beta precludes amyloid formation. Failure to sequester A beta in Alzheimer disease may result in amyloidosis. When we added A beta to cerebrospinal fluid of patients and controls it was rapidly sequestered into stable complexes with transthyretin. Complexes with apolipoprotein E, which has been shown to bind A beta in vitro, were not observed in cerebrospinal fluid. Additional in vitro studies showed that both purified transthyretin and apolipoprotein E prevent amyloid formation.
authors.affiliation: Department of Psychiatry, School of Medicine, State University of New York at Stony Brook 11794.
authors.forename: A L
authors.initials: AL
authors.lastname: Schwarzman
authors.forename: L
authors.initials: L
authors.lastname: Gregori
authors.forename: M P
authors.initials: MP
authors.lastname: Vitek
authors.forename: S
authors.initials: S
authors.lastname: Lyubski
authors.forename: W J
authors.initials: WJ
authors.lastname: Strittmatter
authors.forename: J J
authors.initials: JJ
authors.lastname: Enghilde
authors.forename: R
authors.initials: R
authors.lastname: Bhasin
authors.forename: J
authors.initials: J
authors.lastname: Silverman
authors.forename: K H
authors.initials: KH
authors.lastname: Weisgraber
authors.forename: P K
authors.initials: PK
authors.lastname: Coyle
mesh_terms: D000595:Amino Acid Sequence; D017772:Amyloid Neuropathies / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D003196:Computer Graphics; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011228:Prealbumin / Q000134:cerebrospinal fluid / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D016229:Amyloid beta-Peptides; D011228:Prealbumin