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.
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Acknowledgments
We thank Dr Vanessa Young for assistance with preparation of the tissue sections. Dr Peter Davies and Dr Peter Seubert generously provided antibodies. Tissues were received from the Australian Brain Donor Programs Prince of Wales Medical Research Institute Tissue Resource Centre, which is supported by the National Health and Medical Research Council of Australia and from the Cambridge Brain Bank. This research was supported by grants to J. Götz. from The University of Sydney, The Medical Foundation (University of Sydney), the National Health and Medical Research Council, Judith Jane Mason & Harold Stannett Williams Memorial Foundation, the Australian Research Council and New South Wales Government through the Ministry for Science and Medical Research (BioFirst Grant), and to L.M. Ittner from the Australian Research Council, the University of Sydney and the Deutsche Forschungsgesellschaft and the National Health and Medical Research Council (JK, LI, JG, GH). J. Götz is a Medical Foundation Fellow and G.M. Halliday is a National Health and Medical Research Council Principal Research Fellow. The authors declare that they have no conflict of interest.
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van Eersel, J., Bi, M., Ke, Y.D. et al. Phosphorylation of soluble tau differs in Pick’s disease and Alzheimer’s disease brains. J Neural Transm 116, 1243–1251 (2009). https://doi.org/10.1007/s00702-009-0293-y
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DOI: https://doi.org/10.1007/s00702-009-0293-y