Brain and Plasma Molecular Characterization of the Pathogenic TBI-AD Interrelationship in Mouse Models
Abstract
Traumatic Brain Injury (TBI), in particular mild TBI (mTBI) is a major cause of disability in military and in civilian populations, and for many years has been known to be an epigenetic risk factor for Alzheimers Disease (AD) and other neurodegenerative conditions such as Parkinsons disease, Amyotrophic Lateral Sclerosis or Chronic Traumatic Encephalopathy (CTE) (Randolph, 2001; Gaetz and Weinberg, 2000; Gaetz et al., 2000; Guskiewicz et al., 2003; Gavett et al., 2011; Van Den Heuvel et al., 2007a; Gavett et al., 2010; Frstl et al., 2010; McKee et al.,2009; Costanza et al., 2011; Stern et al., 2011). The existence of a TBI-AD relationship is well recognized (Guo et al., 2000; Jellinger et al., 2001;Mauri et al., 2006; Mayeux et al., 1993; Mayeux et al., 1995; Schofield et al., 1997; Tang et al., 1996; Van Den Heuvel et al., 2007b; Blyth and Bazarian, 2010; Czonkowska and Kurkowska-Jastrzbska, 2011; Hinkebein et al., 2003; Sivanandam and Thakur, 2012; Verghese et al., 2011),and the overlaps and distinctions between pathological features of AD and TBI, including (more recently) CTE, have long been the subject of reporting and discussion (Tokuda et al., 1991; Graham et al., 1995; Irving et al., 1996; Geddes et al., 1996; Geddes et al., 1999; Jellinger et al.,2001; Schmidt et al., 2001; Smith et al., 2003; Uryu et al., 2007; Dekosky et al., 2007; McKee et al., 2009; Magnoni and Brody, 2010; Johnson etal., 2011; Magnoni et al., 2011; Shively et al., 2012; Johnson et al., 2013; McKee et al., 2013; Omalu et al., 2011). However, the precise nature of how TBI leads to or precipitates AD pathogenesis is not understood. The goal of this proposal is to use molecular level approaches in relevant animal models to identify overlapping profiles between TBI and AD and determine early critical cellular responses to TBI that can be targeted for therapeutic intervention.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2015
- Accession Number
- AD1006759
Entities
People
- Fiona Crawford