Down-Regulation of Olfactory Receptors in Response to Traumatic Brain Injury Promotes Risk for Alzheimers Disease
Technical Report,25 Sep 2012,24 Sep 2015
Mount Sinai School of Medicine New York United States
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Traumatic Brain Injury TBI is a risk factor for subsequent development of Alzheimers disease AD. Abnormal tau processingis a common pathological feature of TBI and AD, and tau neuropathology plays a key role in both TBI complications and AD dementia. We recently found aberrant down-regulation of specific olfactory receptors ORs as biological indices for TBI. Moreover, our feasibility evidence suggests that that down-regulation of OR TBI biomarkers following TBI may contribute to TBI-related tau neuropathology. Our proposed studies were designed to investigate whether down-regulation of select OR TBI biomarkers in the brain maycontribute to the elevation of tau neuropathological phenotypes, thereby promoting the development of AD dementia among OperationEnduring Freedom OEF and Operation Iraqi Freedom OIF veterans with exposure to TBI. Our proposed studies were designed to be executed with two Aims. Our proposed Specific Aim 1 studies were designed to develop neuronal culture systems with overexpression of specific OR TBI biomarkers and then, using these novel in vitro experimental models, to screen for selective pharmacological OR activators and to investigate the role of OR biomarkers in tau processing. Our proposed SpecificAim 2 studies were designed to use a recently developed blast-induced mild TBI bTBI rat model to investigate the association betweenexposure to TBI, OR expression and abnormal tau processing, in vivo.