Basic Science and Pathogenesis

Area of Science:

• Neuroscience
• Neuropathology

Background:

• Chronic traumatic encephalopathy (CTE) is linked to brain tau pathology, but spinal cord protein abnormalities are poorly understood.
• CTE often co-occurs with other neurodegenerative diseases, complicating diagnosis and understanding.

Purpose of the Study:

• To investigate the presence and characteristics of misfolded protein pathology in the spinal cords of individuals with CTE.
• To compare spinal cord pathology in CTE with Alzheimer's disease (AD) and control cases.

Main Methods:

• Spinal cord tissues from 28 cases (14 CTE, 6 AD, 1 repetitive head impact, 7 controls) were analyzed using immunohistochemistry.
• Specific markers targeted included phosphorylated tau (p-tau), TDP-43, alpha-synuclein (α-Syn), and amyloid-beta (Aβ).

Main Results:

• Misfolded protein deposition was prevalent in CTE spinal cords: p-tau (100%), Aβ (93%), p-TDP-43 (64%), and α-Syn (50%).
• Prominent astrocytic tau pathology was observed in 86% of CTE cases, a feature absent in AD and controls.
• Brain-spinal cord discrepancies in Aβ deposition were noted, and α-Syn pathology in the spinal cord correlated with Lewy body pathology in the brain.

Conclusions:

• Repetitive traumatic events can induce tau pathology in the spinal cord, in addition to the brain.
• Astrocytic tau pathology in the spinal cord is a potential unique biomarker for CTE.
• The co-occurrence of multiple misfolded proteins in CTE spinal cords suggests a broader impact of repetitive head trauma on protein aggregation.