Traumatic Brain Injury (TBI) Induces Down‐Regulation of Olfactory Receptors That Are Ectopically Expressed In The Brain: Implications In TBI‐Mediated Tauopathy

Abstract

Traumatic brain injury (TBI) is a risk factor for Alzheimer's disease (AD). Tau‐related neuropathology is a key feature of both TBI and AD. We recently identified ectopic expression of selective olfactory receptors (OR) in peripheral blood mononuclear cells (PBMC) and in the brain. We demonstrated that reduced contents of certain ORs in PBMC may serve as biological surrogates (biomarkers) of TBI. Moreover, we found significantly reduced contents of OR biomarkers in post‐mortem brain specimens of cases with a history of TBI. Exploring the potential role of OR biomarkers in the regulation of abnormal tau processing, we found overexpression and activation of an OR biomarker in primary cortico‐hippocampal neurons significantly attenuates pathophysiological tau paired helical filament immunoreactivity. Thus, down regulation of certain OR biomarkers in the brain may causally promote pathophysiological mechanisms underlying TBI clinical complications and, possibly, increase risk of TBI patient to develop AD. Our evidence provides clinically accessible biomarkers for assessing the likelihood of TBI subjects to develop clinical complications, providing more sensitive outcome measurements for clinical interventions and, ultimately, the characterization of potential novel therapeutic targets to prevent TBI‐associated tauopathy.Supported by Department of Defense: Award W81XWH‐08‐2‐0026 to GMP