Abstract

Repetitive head injury in athletes has been increasingly linked to the development of chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disorder. However, its underlying pathobiology remains poorly understood, and definitive diagnosis requires post-mortem examination due to the absence of established in-life biomarkers. Here, we report the neuropathological findings in a retired elite rugby union player with a prolonged history of repetitive head impacts and progressive behavioral changes in the decade preceding his death at the age of 60. The clinical course was characterized by gradually progressive behavioral and affective disturbance in the absence of overt cognitive impairment. Neuropathological findings were consistent with stage IV CTE, with phosphorylated tau (p-Tau) deposition involving neocortical, hippocampal, and midbrain regions, and exhibiting a characteristic distribution in the sulcal depths and perivascular zones. No β-amyloid, α-synuclein, or TDP-43 pathology was identified, suggesting the absence of coexistent neurodegenerative tauopathies. Analysis of blood-brain barrier (BBB) integrity demonstrated reduced claudin-5 immunoreactivity and diffuse immunoglobulin G extravasation in the sulcal depths, overlapping with dense p-Tau deposition, suggestive of BBB dysfunction. To our knowledge, this is the first description of BBB alterations in a case of CTE without dementia or evidence of a coexisting neurodegenerative disease. While based on a single case, warranting cautious interpretation, these findings add to accumulating evidence suggesting that BBB alteration may represent a hallmark feature of CTE.

*These authors contributed equally to this work

Author Details

Authors

• Jeff Henderson¹
• Adam McGlinchey¹
• Bríd Murphy²
• Aoife Canney³
• Matthew Campbell^{1, 4}*
• Michael Farrell⁵*

Departments

• ¹ Smurfit Institute of Genetics, School of Genetics and Microbiology,
• ² Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin,
• ³ Department of Pathology, University Hospital, Galway,
• ⁴ FutureNeuro Research Ireland Centre, Smurfit Institute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, and
• ⁵ Department of Neuropathology, Beaumont Hospital, Dublin, Ireland

Address

Prof. Matthew Campbell
Smurfit Institute of Genetics
School of Genetics and Microbiology
Trinity College Dublin
Dublin 2, DO9 V2NO Ireland
or
Dr. Michael Farrell
Department of Neuropathology
Beaumont Hospital
Dublin, DO9 V2NO Ireland
Email: [email protected]; [email protected]

Citation