Altered phosphorylation but no neurodegeneration in a mouse model of tau hyperphosphorylation

Hundelt, M., Fath, T., Selle, K., Oesterwind, K., Jordan, J., Schultz, C., Götz, J., von Engelhardt, J., Monyer, H., Lewejohann, L., Sachser, N., Bakota, L. and Brandt, R. (2011) Altered phosphorylation but no neurodegeneration in a mouse model of tau hyperphosphorylation. Neurobiology of Aging, 32 6: 991-1006. doi:10.1016/j.neurobiolaging.2009.06.007

Author Hundelt, M.
Fath, T.
Selle, K.
Oesterwind, K.
Jordan, J.
Schultz, C.
Götz, J.
von Engelhardt, J.
Monyer, H.
Lewejohann, L.
Sachser, N.
Bakota, L.
Brandt, R.
Title Altered phosphorylation but no neurodegeneration in a mouse model of tau hyperphosphorylation
Journal name Neurobiology of Aging   Check publisher's open access policy
ISSN 0197-4580
Publication date 2011-01-01
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.neurobiolaging.2009.06.007
Open Access Status Not yet assessed
Volume 32
Issue 6
Start page 991
End page 1006
Total pages 16
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Abstract The role of hyperphosphorylation of tau in Alzheimer's disease is still unsolved. Here we describe a novel transgenic mouse model, expressing a pseudohyperphosphorylated (PHP) variant of the longest human CNS tau isoform in forebrain neurons. We report that pseudohyperphosphorylation decreases phosphorylation at T205 while other sites (T212, S262) are less or not affected compared to mice expressing wildtype tau. Despite the differences in phosphorylation, the subcellular distribution of tau is not affected and mice do not develop highly aggregated states of tau. PHP tau expressing mice do not show any evidence for neurodegeneration as determined from morphometric measurements of neocortical regions, caspase activation, analysis of mitochondrial dysfunction, or determination of spine densities. In agreement, no differences in learning and memory are observed. The data indicates that moderate levels of modified tau alone are not sufficient to induce tau aggregation or neurodegeneration in transgenic mice. With our model it becomes possible to study the effects of hyperphosphorylation at conditions which may prevail in an early preaggregation state of the disease.
Keyword Degeneration
Tau protein
Transgenic mouse
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID SCHU 1412/2-1
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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