[Abstract Title]. - Society for Neuroscience

Poster
245. Tau and Alzheimer's disease
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 245.3/N9
Topic: C.01.h. Tau
Support: Cure Alzheimer‟s Fund
NIH NS049237
Burroughs Wellcome Career Award in the Biomedical Sciences
NIH AG13956
Title: Towards understanding the link between traumatic brain injury and alzheimer‟s disease:
amyloid beta and tau pathologies in an experimental traumatic brain injury mouse model
Authors: *H. T. TRAN 1 , S. ODDO 3 , F. M. LAFERLA 3 , D. M. HOLTZMAN 2 , D. L. BRODY 2 ;
1 Biol. and Biomed. Sci., 2 Neurol., Washington Univ. St Lo, St Louis, MO; 3 Neurobio. &
Behavior, Univ. of California, Irvine, Irvine, CA
Abstract: Traumatic brain injury (TBI) is one of the epidemiological factors predisposing a
person to developing Alzheimer‟s disease (AD) later in life. Neurofibrillary tangles (NFTs) and
neuritic plaques are two pathological hallmarks of AD; both have been observed in human
patients with TBI. To date, the mechanisms underlying the association between TBI and AD
remain unknown. This is in part due to the lack of an appropriate small animal model which
recapitulates the pathologies observed in human patients with TBI. Here, we set out to develop
such a model. We performed controlled cortical impact (CCI), an established experimental TBI
paradigm, on 3xTg-AD mice which express human forms of amyloid precursor protein (APP)
and tau, the main components of plaques and NFTs, respectively. Animals at 6 months of age
were utilized since they have not yet developed prominent amyloid beta (Aβ) and tau
pathologies. This is analogous to young human TBI patients who do not typically have plaques
and NFTs prior to injury. Using immunohistochemistry, western blotting, and ELISA, we
demonstrated that animals which have undergone TBI exhibited exacerbated Aβ and tau
pathologies, as compared to sham injured animals. We observed intracellular immunoreactivity
for Aβ in the ipsilateral fimbria of injured mice only. Aβ immunoreactive axonal varicosities
were also immunoreactive for APP and PS1, a component of the γ-secretase machinery. In
addition, we confirmed there was an increase in total Aβ levels in hippocampal lysates of injured
mice via ELISA and western blots. Interestingly, there was a 50% increase in total tau
immunoreactivity in hippocampal CA1 regions contralateral to impact site. PHF1 (phospho-tau
at residues S396 and S404) immunoreactivity was also observed in the in fimbria, corpus
collosum, and pericontusional areas of injured animals. Previous studies have demonstrated that