Open Access Highly Accessed Research article

Hirano bodies differentially modulate cell death induced by tau and the amyloid precursor protein intracellular domain

William Spears1, Matthew Furgerson12, John Michael Sweetnam1, Parker Evans1, Marla Gearing3, Marcus Fechheimer1 and Ruth Furukawa1*

Author Affiliations

1 Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA

2 Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA

3 Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA

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BMC Neuroscience 2014, 15:74  doi:10.1186/1471-2202-15-74

Published: 14 June 2014



Hirano bodies are actin-rich paracrystalline inclusions found in brains of patients with Alzheimer’s disease (AD), frontotemporal dementia (FTD), and in normal aged individuals. Although studies of post-mortem brain tissue provide clues of etiology, the physiological function of Hirano bodies remains unknown. A cell culture model was utilized to study the interactions of mutant tau proteins, model Hirano bodies, and GSK3β in human astrocytoma cells.


Most tau variants showed co-localization with model Hirano bodies. Cosedimentation assays revealed this interaction may be direct, as recombinant purified forms of tau are all capable of binding F-actin. Model Hirano bodies had no effect or enhanced cell death induced by tau in the absence of amyloid precursor protein intracellular domain (AICD). In the presence of AICD and tau, synergistic cell death was observed in most cases, and model Hirano bodies decreased this synergistic cell death, except for forms of tau that caused significant cell death in the presence of Hirano bodies only. A role for the kinase GSK3β is suggested by the finding that a dominant negative form of GSK3β reduces this synergistic cell death. A subset of Hirano bodies in brain tissue of both Alzheimer’s disease and normal aged individuals was found to contain tau, with some Hirano bodies in Alzheimer’s disease brains containing hyperphosphorylated tau.


The results demonstrate a complex interaction between tau and AICD involving activation of GSK3β in promoting cell death, and the ability of Hirano bodies to modulate this process.

Hirano bodies; Actin; Tau; Amyloid precursor protein; Neurodegeneration; Alzheimer’s disease; Frontotemporal dementia