Abstract: Aggregated Tau protein is associated with over 20 neurological disorders including Alzheimer's disease. Previous work has shown that Tau's sequence segments VQIINK (SEQ ID NO: 11) and VQIVYK (SEQ ID NO: 9) drive its aggregation, and that inhibitors based on the structure of the VQIVYK (SEQ ID NO: 9) segment partially inhibit Tau aggregation. Here we show that the VQIINK (SEQ ID NO: 11) segment is the more powerful driver of Tau aggregation. Two structures of this segment determined by the cryo EM method MicroED explain its more powerful seeding. Of practical significance, the understanding of the structures has led to the design of structure based peptide inhibitors that effectively inhibit Tau aggregation as well as the ability of exogenous Tau fibrils to seed intracellular Tau in mammalian cells into amyloid.

Abstract: Aggregated Tau protein is associated with over 20 neurological disorders including Alzheimer's disease. Previous work has shown that Tau's sequence segments VQIINK and VQIVYK drive its aggregation, and that inhibitors based on the structure of the VQIVYK segment partially inhibit Tau aggregation. Here we show that the VQIINK segment is the more powerful driver of Tau aggregation. Two structures of this segment determined by the cryo EM method MicroED explain its more powerful seeding. Of practical significance, the understanding of the structures has led to the design of structure based peptide inhibitors that effectively inhibit Tau aggregation as well as the ability of exogenous Tau fibrils to seed intracellular Tau in mammalian cells into amyloid.

Abstract: An apparatus, for simultaneously separating multiple samples into their constituents, includes a column manifold which has a plate with a plurality of apertures therethrough. A plurality of support tubes extend from the plate and each support tube has a passage in communication with one of the apertures. The column manifold also includes a fitting to which a vacuum source can the connected, thus enabling the apparatus to be used with both a centrifuge and a vacuum source. A separate separation column is removably received in each support tube and projects through the associated aperture. A collection plate has a plurality of wells arranged so that each well is aligned with a different support tube when the column manifold is placed against the collection plate. This alignment enables each well to receive material expelled from the separation column received in the corresponding support tube.