Recent Advances in Chronic Traumatic Encephalopathy.

Area of Science:

• Neuroscience
• Neuropathology
• Sports Medicine

Background:

• Repeated head impacts (RHIs) are linked to chronic traumatic encephalopathy (CTE), a progressive neurodegenerative tauopathy.
• CTE is currently only diagnosable through post-mortem neuropathologic examination.
• The characteristic lesion of CTE involves perivascular accumulation of hyperphosphorylated tau, particularly in cortical sulci depths.

Purpose of the Study:

• To elucidate the neuropathologic features and biomechanical underpinnings of CTE.
• To explore the relationship between RHI exposure and CTE risk and severity.
• To investigate the association of RHI with other neurodegenerative proteinopathies.

Main Methods:

• Review of neuropathologic findings in CTE.
• Analysis of biomechanical forces associated with RHIs.
• Examination of dose-response relationships between RHI exposure and CTE in athletes.
• Assessment of co-pathologies with other protein aggregations.

Main Results:

• CTE pathology is characterized by unique tau molecular structure, pattern, and distribution.
• A dose-response relationship exists between years of contact sport exposure and CTE risk/severity.
• RHIs also promote deposition of β-amyloid, α-synuclein, and TDP-43, increasing risk for other neurodegenerations.

Conclusions:

• CTE is a distinct tauopathy resulting from RHIs, with diagnosis requiring post-mortem analysis.
• The biomechanics of RHIs, particularly rotational forces in sulci, contribute to tau pathology.
• RHI exposure may predispose individuals to a spectrum of neurodegenerative diseases beyond CTE.