Research Grant - 2008

Brain Injury Award funded by Rosemary Palmer Brown and Robert W Harvey Estates
Assessment of the neuroprotective properties of the amlyoid precursor protein (AAP) following brain injury.

Dr Corinna Van Den Heuvel
University of Adelaide
Co-Investigators: Professor Peter Blumbergs and Ms Frances Corrigan

There is increased expression of the amyloid precursor protein (APP) following traumatic brain injury (TBI). A number of investigators assumed this increase to be detrimental as it may lead to the over-production of one of it’s cleavage products amyloid beta (Ab) and thus potentially lead to Alzheimer’s Disease (AD). However, there is also evidence to suggest that APP has many beneficial effects within the central nervous system. Our previous studies showed that administration of APP shortly after trauma, in a rodent head injury model, significantly protects against neuronal damage and improves outcome following TBI. These results subsequently prompted a collaboration between the University of Melbourne scientists who have extensive expertise in APP biology with our University of Adelaide group who have expertise in experimental models of neurotrauma.

This study will be the first to directly examine the role of endogenous APP in TBI by using APP knockout mice in a TBI model to further support the role APP plays in protecting neurons following TBI. We predict that the lack of APP expression in these mice will make neurons more vulnerable to head injury and these mice will have a poorer neurological outcome following TBI. The second key outcome of these studies is to administer different regions of synthesized APP into the brain following TBI in order to identify the active (neuroprotective) region of exogenously administered APP. This second aim will facilitate developing APP into a therapeutic agent for treating neurotrauma in humans by developing either peptide analogues or synthetic organic compounds that mimic the active region of the APP molecule.