Abstract
In addition to tau hyperphosphorylation, tau truncation is also detected in Alzheimer’s disease (AD) patients. In the brain of AD transgenic mouse models, the pathological details of truncated tau are not well characterized. In this study, we analyzed spatial relationships among tau truncation, tau phosphorylation and neurodegeneration or tangle formation in a tauP301L single transgenic mouse model and a triple transgenic mouse model that produces both amyloid plaques, and neurofibrillary tangles. During development of tau pathology, the spatial relationship between hyperphosphorylation and truncation of tau exhibited a shift from colocalization at low densities of hyperphosphorylated tau to partial dissociation at high densities. Importantly, we detected a few neurons that contained abundant truncated tau but were lacking hyperphosphorylation, and these neurons exhibited remarkable nuclear condensation. In the case of colocalization, truncated tau was commonly associated with high immunoreactivity of hyperphosphorylated tau and dense Gallyas silver staining. Taken together, our study shows that tau truncation appears after tau hyperphosphorylation in the brain of two transgenic mouse models, and that accumulation of truncated tau, in the absence or the presence of phosphorylated tau, is closely associated with a subset of neurons undergoing degeneration or containing neurofibrillary tangles.
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Acknowledgments
We thank K.P. Lu and D. Saffen for critical comments on this study. This work was supported by grants from the National Natural Science Foundation of China (30470594, 30772282), the Shanghai Science and Technology Committee (07DJ14005), and the Basic Research Program of China (973) (2007CB507400).
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Zhang, Q., Zhang, X. & Sun, A. Truncated tau at D421 is associated with neurodegeneration and tangle formation in the brain of Alzheimer transgenic models. Acta Neuropathol 117, 687–697 (2009). https://doi.org/10.1007/s00401-009-0491-6
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DOI: https://doi.org/10.1007/s00401-009-0491-6