Original Paper

Acta Neuropathologica

, Volume 117, Issue 6, pp 687-697

Truncated tau at D421 is associated with neurodegeneration and tangle formation in the brain of Alzheimer transgenic models

  • Qipeng ZhangAffiliated withInstitute of Neurobiology, State Key Laboratory of Medical Neurobiology, Fudan University
  • , Xiaoguang ZhangAffiliated withDepartment of Anesthesiology, Zhongshan Hospital, Fudan University
  • , Anyang SunAffiliated withInstitute of Neurobiology, State Key Laboratory of Medical Neurobiology, Fudan University Email author 

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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.

Keywords

Alzheimer’s disease Tau truncation Tau phosphorylation Neurodegeneration Neurofibrillary tangles