Characterization of Prefibrillar Tau Oligomers in Vitro and in Alzheimer Disease

• DOI: 10.1074/jbc.m111.237974
• Publication Date: 2011-05-07T00:19:27Z
• Authors: Kristina R. Patte...; Christine Remmers; Yifan Fu; Sarah Brooker; Nicholas M. Kanaan; Laurel Vana; Sarah Ward; Juan F. Reyes; Keith Philibert; Marc J. Glucksman; Lester I. Binder
• Keywords: Tau protein; Immunostaining; Pathogenesis

Neurofibrillary tangles, composed of insoluble aggregates the microtubule-associated protein Tau, are a pathological hallmark Alzheimer disease (AD) and other tauopathies. However, recent evidence indicates that neuronal dysfunction precedes formation these fibrillar deposits, suggesting earlier prefibrillar Tau may be neurotoxic. To determine composition aggregates, we have employed photochemical cross-linking technique to examine intermolecular interactions full-length in vitro. Using this method, demonstrate dimerization is an early event aggregation process dimers self-associate form larger oligomeric aggregates. Moreover, using stabilized as immunogens, generated monoclonal antibody selectively recognizes higher order but shows little reactivity filaments Immunostaining dimers/oligomers markedly elevated AD, appearing inclusions such neuropil threads pretangle neurons well colocalizing with markers pathogenesis. Taken whole, work presented herein demonstrates existence alternative precede pathologies raises possibility hierarchical forms contribute neurodegeneration.