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

Spiro Anthony Stathas, Victor E. Alvarez, Weiming Xia, Raymond Nicks, Gaoyuan Meng, Sarah Daley, Morgan Pothast, Arsal Shah, Hunter Kelley, Camille Esnault, Robert McCormack, Erin Dixon, Lucas Fishbein, Jonathan D. Cherry, Bertrand R. Huber, Yorghos Tripodis, Michael L. Alosco, Jesse Mez, Ann C. McKee, Thor D. Stein

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1511-1522
Number of pages12
JournalAlzheimer's and Dementia
Volume18
Issue number8
DOIs
StatePublished - Aug 2022

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
  • tau Proteins/metabolism
  • Phosphorylation
  • Chronic Traumatic Encephalopathy
  • Humans
  • Alzheimer Disease/complications
  • Amyloid beta-Peptides/metabolism

ASJC Scopus subject areas

  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Health Policy
  • Developmental Neuroscience
  • Epidemiology

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