P018
A detailed longitudinal assessment of pathology in male
and female rTg4510 tau transgenic mice.
Katya Malfa1, Claire V. Cella1, Hannah Clarke1,
Mark A. Ward1, Dan L. Czilli2, Tracey K. Murray1,
Michael L. Hutton1 and Michael J. O’Neill1
1
Eli Lilly & Co Ltd, Windlesham, United Kingdom
2
Eli Lilly & Co. Ltd., Indianapolis, U.S.A.
Hyperphosphorylation and formation of insoluble aggregates of
tau are common features of all human tauopathies. In this study
we characterised the temporal changes in tau pathology in male
and female non-transgenic and rtg4510 tau mice at 2, 4, 6, 8
and 10 months of age. Brains were removed and weighed and
immunocytochemistry carried out using a panel of tau antibodies
including MC-1, AT-8, PHF-1, PG-5, nY29 as well as neuronal
(NeuN) and microglial (IBA-1) markers. The results indicated that
there was a progressive pattern of tau pathology in this model.
There was no tau tangle pathology at 2 months, but there was
evidence for MC-1 positive staining in the forebrain. There was
a large increase in aggregated tau and tangle formation in the
forebrain at 4 months of age and an inflammatory response was
also evident. At 6 and 8 months of age there was robust tau
pathology, clear evidence for brain shrinkage and neurodegeneration in both the hippocampus and cortex. The tau pathology
was more pronounced in female mice. In addition, the number
of AT-8 and PG5 positive cells appeared to correlate with the
degree of brain shrinkage observed at 4, 6 and 8 months of age.
In summary our data indicate that the rtg4510 model represents
a very useful model to study the progressive stages of tau
pathology that are similar to those observed in the AD brain.