S2–02–05: Neuritic alterations and dysfunctions in Alzheimer's disease

not available. S2-03-06 FUNCTIONAL AND STRUCTURAL ANALYSIS OF -SECRETASE Harald Steiner, Edith Winkler, Aya Yamasaki, Keiro Shirotani, Blanca Perez Revuelta, Masanori Tomioka, Christian Haass, LudwigMaximilians-University, Adolf-Butenandt-Institute, Munich, Germany. Contact e-mail: hsteiner@med.uni-muenchen.de Background: -Secretase catalyzes the intramembrane cleavage of a large variety of type I membrane proteins including the Alzheimer s disease -amyloid precursor protein. Biochemical and genetic studies demonstrated that -secretase is a complex composed of presenilin (PS), nicastrin (NCT), APH-1 and PEN-2. In human cells, two PS homologues, PS1 and PS2, and two APH-1 homologues, APH-1a and APH-1b, were identified and shown to be part of distinct -secretase complexes demonstrating that -secretase represents a heterogeneous activity. Apart from the established role of PS as the catalytic subunit of -secretase and the recently proposed role of NCT as substrate receptor, knowledge about the function of the other subunits within the complex, in particular regarding the mechanism S27 Symposia S2-03: Disease Mechanisms (Presenilins/ -Secretase)