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

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-tau 231 , and p-tau 396 were significantly increased in CTE. Total years of RHI exposure was significantly associated with increased p-tau 202 levels (P = .001), but not p-tau 396 . Instead, p-tau 396 was most closely related to amyloid beta (Aβ) 1-42 levels (P < .001). The p-tau 202 :p-tau 396 ratio was significantly increased in early and late CTE compared to AD.

DISCUSSION: In frontal cortex, p-tau 202 is the most upregulated p-tau species in CTE, while p-tau 396 is most increased in AD. p-tau 202 and p-tau 396 measurements may aid in developing biomarkers for disease.