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Hyperphosphorylation determines both the spread and the morphology of tau pathology
Author(s) -
Hu Wen,
Zhang Xinhua,
Tung Yunn Chyn,
Xie Shutao,
Liu Fei,
Iqbal Khalid
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.01.014
Subject(s) - tau pathology , hyperphosphorylation , tauopathy , neocortex , tau protein , pathology , hippocampus , neuroscience , hippocampal formation , synaptophysin , genetically modified mouse , biology , neurodegeneration , chemistry , alzheimer's disease , phosphorylation , medicine , transgene , microbiology and biotechnology , immunohistochemistry , disease , biochemistry , gene
Neurofibrillary pathology of abnormally hyperphosphorylated tau (P‐tau) is a hallmark of Alzheimer's disease (AD) and other tauopathies. Tau pathology can be experimentally induced and propagated. However, what induces the prion‐like transmission character to tau and produces morphologically distinct tau lesions remains elusive. Methods We investigated the role of hyperphosphorylation in the spread of tau pathology in hTau transgenic mice. Results We found that intrahippocampal injection with AD P‐tau, but not nonphosphorylated tau, produced numerous P‐tau tangles and neuropil threads locally and in neocortex lateral to injection and upstream to the hippocampus. Dephosphorylation of AD P‐tau with protein phosphatase‐2A dramatically reduced and switched tau pathology from neurofibrillary tangles to argyrophilic grain‐like morphology. Conclusions Our findings show that abnormal hyperphosphorylation of tau determines the spread and morphology of tau lesions and that the propagation of tau pathology takes place both locally and in axonally connected areas and highlight tau hyperphosphorylation as a potential drug target.