TRANSTHYRETIN SEQUESTERS AMYLOID-BETA PROTEIN AND PREVENTS AMYLOID FORMATION

The cardinal pathological features of Alzheimer disease are deposition s of aggregated amyloid beta protein (A beta) in the brain and cerebro vasculature. However, the A beta is found in a soluble form in cerebro spinal fluid in healthy individuals and patients with Alzheimer diseas e. We postulate that sequestration of A beta precludes amyloid formati on. Failure to sequester A beta in Alzheimer disease may result in amy loidosis. When we added A beta to cerebrospinal fluid of patients and controls it was rapidly sequestered into stable complexes with transth yretin. 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 apolipopr otein E prevent amyloid formation.