Tau phosphorylation sites serine202 and serine396 are differently altered in chronic traumatic encephalopathy and Alzheimer's disease

Abstract

Introduction: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impacts (RHI) typically sustained by contact sport athletes. Post-translation modifications to tau in CTE have not been well delineated or compared to Alzheimer's disease (AD).

Methods: We measured phosphorylated tau epitopes within dorsolateral frontal cortex from post mortem brains with neither CTE nor AD (n = 108), CTE (n = 109), AD (n = 223), and both CTE and AD (n = 33).

Results: Levels of hyperphosphorylated tau (p-tau)₂₀₂ , p-tau₂₃₁ , and p-tau₃₉₆ were significantly increased in CTE. Total years of RHI exposure was significantly associated with increased p-tau₂₀₂ levels (P = .001), but not p-tau₃₉₆ . Instead, p-tau₃₉₆ was most closely related to amyloid beta (Aβ)_1-42 levels (P < .001). The p-tau₂₀₂ :p-tau₃₉₆ ratio was significantly increased in early and late CTE compared to AD.

Discussion: In frontal cortex, p-tau₂₀₂ is the most upregulated p-tau species in CTE, while p-tau₃₉₆ is most increased in AD. p-tau₂₀₂ and p-tau₃₉₆ measurements may aid in developing biomarkers for disease.

Keywords: Alzheimer's disease; amyloid beta peptides; brain; chronic traumatic encephalopathy; football; humans; male; microtubule-associated proteins; pathology; statistics and numerical data; tau proteins; tauopathies.