University of Massachusetts Lowell Lowell United States
The goal of this project is project was to increase our understanding of the underlying causes of both CTE and AD and by so doing, improve our ability to diagnose the presence and severity of these conditions in a timely manner. Our approach was based on observations that tau isoforms lacking exons 2-3 in the tau N terminal domain E2- tau are secreted more readily than isoforms that contain one or both of them E2 tau in cell culture Kim et. al. 2010 and that secreted microvesicles exosomes containing tau and other proteins are identifiable in the cerebrospinal fluid CSF of patients, in the early stages of AD Saman et al 2012. The Aims of the project were to 1 characterize the cellular distribution of E2 and E2- tau isoforms in fixed brain tissue from early AD and CTE patients, to quantify their presence in CSF and brain homogenate exosomal fractions and to identify proteins associated with tauand particularly E2- and E2 tau in these fractions in the context of ADCTE cytopathogenesis. The second Aim of this project was to directly test the effects of overexpressing E2- and E2 tau isoforms on tau distribution, secretion and the recruitment of other proteins to exosomes in neuronal cell lines by mass spectrometry.