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Title: Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons
Author: Rodriguez-Rodriguez, Patricia
Sandebring-Matton, Anna
Merino-Serrais, Paula
Parrado-Fernandez, Cristina
Rabano, Alberto
Winblad, Bengt
Avila, Jesús
Ferrer, Isidro (Ferrer Abizanda)
Cedazo-Mínguez, Ángel
Keywords: Malaltia d'Alzheimer
Resistència a la insulina
Alzheimer's disease
Insulin resistance
Issue Date: 1-Dec-2017
Publisher: Oxford University Press
Abstract: Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathological conditions. Here, we report that insulin is accumulated and retained as oligomers in hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of the most prevalent human tauopathies. The intraneuronal accumulation of insulin is directly dependent on tau hyperphosphorylation, and follows the tauopathy progression. Furthermore, cells accumulating insulin show signs of insulin resistance and decreased insulin receptor levels. These results suggest that insulin retention in hyperphosphorylated tau-bearing neurons is a causative factor for the insulin resistance observed in tauopathies, and describe a novel neuropathological concept with important therapeutic implications.
Note: Versió postprint del document publicat a:
It is part of: Brain, 2017, vol. 40, num. 12, p. 3269-3285
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ISSN: 0006-8950
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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