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‐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.