title: Tau causes synapse loss without disrupting calcium homeostasis in the rTg4510 model of tauopathy.
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.
authors.affiliation: Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts, United States of America ; MassGeneral Institute for Neurodegenerative Disease at Massachusetts General Hospital, Charlestown, Massachusetts, United States of America.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Kopeikina
authors.forename: Susanne
authors.initials: S
authors.lastname: Wegmann
authors.forename: Rose
authors.initials: R
authors.lastname: Pitstick
authors.forename: George A
authors.initials: GA
authors.lastname: Carlson
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bacskai
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Betensky
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.forename: Tara L
authors.initials: TL
authors.lastname: Spires-Jones
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism; D004195:Disease Models, Animal; D006706:Homeostasis; D006801:Humans; D051379:Mice; D057054:Molecular Imaging; D013569:Synapses / Q000378:metabolism*; D024801:Tauopathies / Q000378:metabolism* / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D016875:tau Proteins; C495639:yellow cameleon; D002118:Calcium