Chapter 2 - Chronic traumatic encephalopathy and the nucleus basalis of Meynert

Abstract

Due to the growing number of chronic traumatic encephalopathy (CTE) cases in the military and contact sports, defining the cellular and molecular substrate of this disorder is crucial. Most classic neuropathological investigations describe cortical tau and, to a lesser extent, amyloid lesions, which may underlie the clinical sequela associated with CTE. The application of modern molecular biologic technology to postmortem human brain tissue has made it possible to evaluate the genetic signature of specific neuronal phenotypes at different stages of CTE pathology. Most recently, molecular pathobiology has been used in the field of CTE, with an emphasis on the cholinergic neurons located within the nucleus basalis of Meynert, which develop tau pathology and are associated with cognitive dysfunction similar to that found in Alzheimer's disease (AD). Quantitative findings derived from single-cell transcript investigations provide clues to our understanding of the selective vulnerability of neurons containing AD-like tau pathology at different stages of CTE. Since human tissue-based studies provide a gold standard for the field of CTE, continued molecular pathological studies are needed to reveal novel drug targets for the treatment of this disorder.