Journal of Neural Transmission

, Volume 116, Issue 10, pp 1243–1251 | Cite as

Phosphorylation of soluble tau differs in Pick’s disease and Alzheimer’s disease brains

  • Janet van Eersel
  • Mian Bi
  • Yazi D. Ke
  • John R. Hodges
  • John H. Xuereb
  • Gillian C. Gregory
  • Glenda M. Halliday
  • Jürgen Götz
  • Jillian J. Kril
  • Lars M. Ittner
Dementias - Original Article

Abstract

Frontotemporal lobar degeneration (FTLD) is a common cause of presenile dementia characterised by behavioural and language disturbances. Pick’s disease (PiD) is a subtype of FTLD, which presents with intraneuronal inclusions consisting of hyperphosphorylated tau protein aggregates. Although Alzheimer’s disease (AD) is also characterised by tau lesions, these are both histologically and biochemically distinct from the tau aggregates found in PiD. What determines the distinct characteristics of these tau lesions is unknown. As phosphorylated, soluble tau has been suggested to be the precursor of tau aggregates, we compared both the level and phosphorylation profile of tau in tissue extracts of AD and PiD brains to determine whether the differences in the tau lesions are reflected by differences in soluble tau. Levels of soluble tau were decreased in AD but not PiD. In addition, soluble tau was phosphorylated to a greater extent in AD than in PiD and displayed a different phosphorylation profile in the two disorders. Consistently, tau kinases were activated to different degrees in AD compared with PiD. Such differences in solubility and phosphorylation may contribute, at least in part, to the formation of distinct tau deposits, but may also have implications for the clinical differences between AD and PiD.

Keywords

Alzheimer’s disease Frontotemporal lobar degeneration ERK Phosphorylation Pick’s disease Tau 

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Janet van Eersel
    • 1
    • 2
  • Mian Bi
    • 2
  • Yazi D. Ke
    • 2
  • John R. Hodges
    • 3
  • John H. Xuereb
    • 4
  • Gillian C. Gregory
    • 3
  • Glenda M. Halliday
    • 3
  • Jürgen Götz
    • 2
    • 5
  • Jillian J. Kril
    • 1
    • 6
  • Lars M. Ittner
    • 2
  1. 1.Discipline of PathologyThe University of SydneySydneyAustralia
  2. 2.Alzheimer’s and Parkinson’s Disease Laboratory, Brain and Mind Research InstituteThe University of SydneyCamperdownAustralia
  3. 3.Prince of Wales Medical Research InstituteThe University of NSWRandwickAustralia
  4. 4.Department of PathologyUniversity of CambridgeCambridgeUK
  5. 5.The Medical FoundationThe University of SydneyCamperdownAustralia
  6. 6.Discipline of MedicineThe University of SydneySydneyAustralia

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