Chronic Traumatic Encephalopathy

Chronic traumatic encephalopathy (CTE) is a progressive, neurodegenerative tauopathy associated with exposure to repetitive head injury, including concussions and subconcussions. Clinical features of CTE consist of abnormalities in behavior, including explosivity, impulsivity, and suicidality; mood, including depressed mood and hopelessness; cognition, including executive dysfunction, memory loss, and dementia; and movement, including parkinsonism. Neuropathologically, there is often generalized cortical atrophy, which may be most severe in the frontal and temporal lobes; abnormalities of the septum pellucidum, such as cavum septum or fenestrations; enlargement of the lateral and third ventricles; atrophy of the diencephalon; and depigmentation of the substantia nigra and locus coeruleus. Microscopically, CTE is defined by the perivascular accumulation of hyperphosphorylated tau (p-tau) in neurons and neuronal processes as neurofibrillary tangles (NFTs) and disordered neurites and in astrocytes, irregularly distributed in the cerebral cortex, with a predilection for the sulcal depths. In the mildest forms of CTE, a few perivascular CTE lesions are found in the cortex; in advanced CTE, p-tau NFTs and neurites are widely distributed in other cortical regions, often in the superficial layers of cortex, as well as the hypothalamus, thalamus, and brainstem. Most of the knowledge about CTE has been gained from the careful clinical characterization and comprehensive postmortem pathological analysis of brain donors. Although these studies have been essential to understanding the clinicopathological features of CTE and its molecular pathogenesis, current tissue-based research efforts have expanded to include developing in vivo biomarkers and diagnostics, characterizing risk factors, and developing methods to prevent and treat CTE.