Tau pathology in Creutzfeldt-Jakob disease revisited

Brain Pathol. 2017 May;27(3):332-344. doi: 10.1111/bpa.12411. Epub 2016 Aug 2.


Creutzfeldt-Jakob disease (CJD) is a human prion disease with different etiologies. To determine the spectrum of tau pathologies in CJD, we assessed phospho-Tau (pTau) immunoreactivities in 75 sporadic CJD cases including an evaluation of the entorhinal cortex and six hippocampal subregions. Twelve cases (16%) showed only small tau-immunoreactive neuritic profiles. Fifty-two (69.3%) showed additional tau pathology in the medial temporal lobe compatible with primary age related tauopathy (PART). In 22/52 cases the lower pTau immunoreactivity load in the entorhinal cortex as compared to subiculum, dentate gyrus or CA4 region of the hippocampus was significantly different from the typical distribution of the Braak staging. A further 11 cases (14.7%) showed widespread tau pathologies compatible with features of primary tauopathies or the gray matter type of ageing-related tau astrogliopathy (ARTAG). Prominent gray matter ARTAG was also observed in two out of three additionally examined V203I genetic CJD cases. Analysis of cerebrospinal fluid revealed prominent increase of total tau protein in cases with widespread tau pathology, while pTau (T181) level was increased only in four. This correlated with immunohistochemical observations showing less pathology with anti-pTau T181 antibody when compared to anti-pTau S202/T205, T212/S214 and T231. The frequency of tau pathologies is not unusually high in sporadic CJD and does not precisely relate to PrP deposition. However, the pattern of hippocampal tau pathology often deviates from the stages of Braak. Currently applied examination of cerebrospinal fluid pTau (T181) level does not reliably reflect primary tauopathies, PART and ARTAG seen in CJD brains.

Keywords: ARTAG; Creutzfeldt-Jakob disease; PART; cerebrospinal fluid; prion; tau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Biomarkers / cerebrospinal fluid
  • Brain / metabolism
  • Brain / pathology*
  • Creutzfeldt-Jakob Syndrome / complications*
  • Creutzfeldt-Jakob Syndrome / genetics
  • Creutzfeldt-Jakob Syndrome / metabolism
  • Creutzfeldt-Jakob Syndrome / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neurons / metabolism
  • Neurons / pathology
  • Phosphorylation
  • Prion Proteins / genetics
  • Tauopathies / complications*
  • Tauopathies / genetics
  • Tauopathies / metabolism
  • Tauopathies / pathology*
  • tau Proteins / metabolism


  • Biomarkers
  • MAPT protein, human
  • PRNP protein, human
  • Prion Proteins
  • tau Proteins

Supplementary concepts

  • Creutzfeldt-Jakob Disease, Sporadic