Tau causes synapse loss without disrupting calcium homeostasis in the rTg4510 model of tauopathy

Katherine J. Kopeikina; Susanne Wegmann; Rose Pitstick; George A. Carlson; Brian J. Bacskai; Rebecca A. Betensky; Bradley T. Hyman; Tara L. Spires-Jones

doi:10.1371/journal.pone.0080834

Tau causes synapse loss without disrupting calcium homeostasis in the rTg4510 model of tauopathy

Katherine J. Kopeikina, Susanne Wegmann, Rose Pitstick, George A. Carlson, Brian J. Bacskai, Rebecca A. Betensky, Bradley T. Hyman, Tara L. Spires-Jones

Global Public Health

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Abstract

Neurofibrillary tangles (NFTs) of tau are one of the defining hallmarks of Alzheimer's disease (AD), and are closely associated with neuronal degeneration. Although it has been suggested that calcium dysregulation is important to AD pathogenesis, few studies have probed the link between calcium homeostasis, synapse loss and pathological changes in tau. Here we test the hypothesis that pathological changes in tau are associated with changes in calcium by utilizing in vivo calcium imaging in adult rTg4510 mice that exhibit severe tau pathology due to over-expression of human mutant P301L tau. We observe prominent dendritic spine loss without disruptions in calcium homeostasis, indicating that tangles do not disrupt this fundamental feature of neuronal health, and that tau likely induces spine loss in a calcium-independent manner.

Original language	English (US)
Article number	e80834
Journal	PloS one
Volume	8
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0080834
State	Published - Nov 20 2013

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
General

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abstract = "Neurofibrillary tangles (NFTs) of tau are one of the defining hallmarks of Alzheimer's disease (AD), and are closely associated with neuronal degeneration. Although it has been suggested that calcium dysregulation is important to AD pathogenesis, few studies have probed the link between calcium homeostasis, synapse loss and pathological changes in tau. Here we test the hypothesis that pathological changes in tau are associated with changes in calcium by utilizing in vivo calcium imaging in adult rTg4510 mice that exhibit severe tau pathology due to over-expression of human mutant P301L tau. We observe prominent dendritic spine loss without disruptions in calcium homeostasis, indicating that tangles do not disrupt this fundamental feature of neuronal health, and that tau likely induces spine loss in a calcium-independent manner.",

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AU - Kopeikina, Katherine J.

AU - Wegmann, Susanne

AU - Pitstick, Rose

AU - Carlson, George A.

AU - Bacskai, Brian J.

AU - Betensky, Rebecca A.

AU - Hyman, Bradley T.

AU - Spires-Jones, Tara L.

PY - 2013/11/20

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AB - Neurofibrillary tangles (NFTs) of tau are one of the defining hallmarks of Alzheimer's disease (AD), and are closely associated with neuronal degeneration. Although it has been suggested that calcium dysregulation is important to AD pathogenesis, few studies have probed the link between calcium homeostasis, synapse loss and pathological changes in tau. Here we test the hypothesis that pathological changes in tau are associated with changes in calcium by utilizing in vivo calcium imaging in adult rTg4510 mice that exhibit severe tau pathology due to over-expression of human mutant P301L tau. We observe prominent dendritic spine loss without disruptions in calcium homeostasis, indicating that tangles do not disrupt this fundamental feature of neuronal health, and that tau likely induces spine loss in a calcium-independent manner.

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Tau causes synapse loss without disrupting calcium homeostasis in the rTg4510 model of tauopathy

Abstract

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