Tau seeding in chronic traumatic encephalopathy parallels disease severity

Area of Science:

• Neurodegenerative diseases
• Tauopathies
• Neurobiology

Background:

• Chronic traumatic encephalopathy (CTE) is a tauopathy linked to cognitive, mood, and behavioral deficits.
• Tau pathology progression in neurodegenerative diseases may involve templated seeding and transcellular propagation.
• The relationship between tau seeding and phospho-tau deposition in CTE remains unclear.

Purpose of the Study:

• To quantify tau seeding in CTE brain tissue using a biosensor assay.
• To compare tau seeding patterns with AT8 phospho-tau histopathology in CTE.
• To investigate the anatomical distribution of tau seeding in CTE.

Main Methods:

• Utilized a cell-based biosensor assay to detect and quantify tau seeding.
• Analyzed fixed brain tissue from 27 CTE patients, 5 with other tauopathies, and 5 controls.
• Examined 11 brain regions per patient, comparing seeding to AT8 phospho-tau staining.

Main Results:

• Tau seeding was detected late in CTE, primarily in stages III and IV.
• Seeding was less widespread anatomically than AT8-positive inclusions.
• Significant seeding was observed in the limbic system (amygdala, thalamus, basal ganglia).

Conclusions:

• Tau seeding occurs late in CTE, distinct from earlier stages of phospho-tau deposition.
• The limbic system's involvement in tau seeding may underlie CTE-associated cognitive and behavioral symptoms.
• Findings suggest a potential mechanism for tau pathology spread in CTE.