N-Terminal Tau Fragments as Biomarkers for Alzheimer's Disease and Neurotrauma
Abstract
The goal of this project is to identify CSF biomarkers for Alzheimer's Disease (AD) based on known cellular events in AD pathogenesis related to 1) tau secretion and 2) the synergy between AD and repeated traumatic brain injury (chronic traumatic encephalopathy or CTE). The project is intended to increase our understanding of the underlying causes of both CTE and AD as well as improve our ability to diagnose the presence and severity of these conditions in a timely manner. Our approach is based on observations that tau isoforms lacking exon 2-3 (E2- tau) are secreted more readily than E2+ isoforms in cell culture (Kim 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. The Aims of the project are 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 tau (and particularly E2- and E2+ tau) in these fractions in the context of AD/CTE cytopathogenesis. The second Aim of this project is 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). The presence and distribution of proteins identified as potential key players in AD/CTE-associated tau secretion will then be tested in human brain and CSF.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2014
- Accession Number
- ADA623509
Entities
People
- Garth F. Hall
Organizations
- University of Massachusetts Lowell