Chronic Traumatic Encephalopathy: A Brief Overview

Abstract

Chronic Traumatic Encephalopathy (CTE) is a debilitating neurodegenerative disease, which has been increasingly reported in athletes, especially American football players, as well as military veterans in combat settings, commonly as a result of repetitive mild traumatic brain injuries (TBIs). CTE has a unique neuropathological signature comprised of accumulation of phosphorylated tau (p-tau) in sulci and peri-vascular regions, microgliosis, and astrocytosis. As per most recent disease classification, the disease manifests itself in four different stages, characterized by widespread tauopathy. Clinically, CTE has a more subtle presentation, as patients often present with two distinct phenotypes, with one subtype initially presenting with affective changes, and the other subtype with more cognitive impairment. On a genetic basis, there are no clear risk factor genes. Although ApoE4 carriers have been reported to suffer more severe outcome post TBI. As there are no disease modifying regimen for CTE, the newly developed TBI treatments, if administered in a time sensitive manner, can offer a potential viable option. Prevention is another key strategy that needs to be implemented in various sports and military settings. Providing education for safe practice techniques, such as safe tackling and hitting, and providing ready access to full neuropsychiatric assessment by team physician could have measurable benefits. The combination of advanced of research techniques including neuroimaging, as well as increasing public awareness of CTE, offers promising vistas for research advancement.

A Clinicopathological Report of a 93-Year-Old Former Street Boxer With Coexistence of Chronic Traumatic Encephalopathy, Alzheimer's Disease, Dementia With Lewy Bodies, and Hippocampal Sclerosis With TDP-43 Pathology

“…However, the neuronal p-tau found in CTE does share a similar profile regarding isoform ratio and phosphorylation state as the tau in AD (10). Both CTE and AD share the characteristic feature of hyperphosphorylated tau, where phosphorylation at specific residues occurs as an ordered process, leading to tau aggregation and oligomer formation (6). However, in the present case, the severity of CA1-predominant neurofibrillary degeneration in the hippocampus supports the coexistence of AD and CTE (10,22).…”

“…In 2016, the first NINDS/NIBIB consensus meeting defined the neuropathological criteria of CTE and confirmed that the pathognomonic lesions in CTE are accumulations of abnormally hyperphosphorylated tau (p-tau) in astrocytes and neurons located around small blood vessels and at the depths of the cortical sulci (10). CTE, a new neurodegenerative tauopathy, was reported in athletes who played soccer, baseball, ice hockey, and rugby, as well as in military personnel exposed to explosive blasts (5)(6)(7)11). Clinical presentation of CTE was divided into three phases: behavioral/psychiatric, cognitive, and motor (12,13).…”

“…Traumatic brain injury (TBI) was long recognized as a risk factor for dementia (1)(2)(3)(4)(5). Chronic traumatic encephalopathy (CTE) refers to the neuropathological changes resulting from repeated episodes of TBI (3,(5)(6)(7). In the early twentieth century, the terms "punch-drunk" or "dementia pugilistica" were used to describe the clinical features of a distinct neuropsychiatric syndrome that affected boxers.…”

Hyperphosphorylated tau aggregation and cytotoxicity modulators screen identified prescription drugs linked to Alzheimer's disease and cognitive functions

“…This drug is therefore not ideal for AD treatment. On the other hand, it has been reported that a spike of tau hyperphosphorylation happens after brain injury 76 and general anesthesia 77 , due likely to acutely diminished phosphatase activities 78,79 . Whether this transient tau hyperphosphorylation is related to the positive association between dementia and traumatic brain injury 13 or exposure to general anesthesia 80 remains an open question.…”

Will Sirtuins Be Promising Therapeutic Targets for TBI and Associated Neurodegenerative Diseases?

“…For example, moderate or severe TBI contributes to the development of late-onset neurodegenerative diseases, in particular AD and PD (Mendez, 2017). Chronic traumatic encephalopathy (CTE), a condition that shares features with neurodegenerative diseases, is linked to mild TBI (Fesharaki-Zadeh, 2019). Numerous random-effects meta-analysis (Perry et al, 2016), epidemiologic study (Gardner and Yaffe, 2015), and retrospective cohort study (Gardner et al, 2018) have lent support to these associations.…”