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. 2016 Oct;12(10):1066-1077.
doi: 10.1016/j.jalz.2016.01.014. Epub 2016 Apr 28.

Hyperphosphorylation determines both the spread and the morphology of tau pathology

Wen Hu  1 , Xinhua Zhang  2 , Yunn Chyn Tung  1 , Shutao Xie  2 , Fei Liu  3 , Khalid Iqbal  4
Affiliations

Hyperphosphorylation determines both the spread and the morphology of tau pathology

Wen Hu et al. Alzheimers Dement. 2016 Oct.

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Alzheimers Dement. 2017 Apr;13(4):498. doi: 10.1016/j.jalz.2017.03.004. Alzheimers Dement. 2017. PMID: 28400031 No abstract available.

Abstract

Introduction: 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.

Keywords: Alzheimer's disease; Argyrophilic grains; Prion-like spread; Protein phosphatase-2A; Tau hyperphosphorylation; Tauopathies.

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