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Cell Press, Neuron, 2(76), p. 461, 2012

DOI: 10.1016/j.neuron.2012.10.005

Cell Press, Neuron, 4(73), p. 685-697, 2012

DOI: 10.1016/j.neuron.2011.11.033

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Propagation of tau pathology in a model of early Alzheimer’s disease

Journal article published in 2012 by Alix de Calignon, Manuela Polydoro, Marc Suárez-Calvet ORCID, Christopher William, David H. Adamowicz, Kathy J. Kopeikina, Rose Pitstick, Karen H. Ashe, Naruhiko Sahara, George A. Carlson, Tara L. Spires-Jones, Bradley T. Hyman
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Neurofibrillary tangles advance from layer II of the entorhinal cortex (EC-II) toward limbic and association cortices as Alzheimer disease (AD) evolves. However, the mechanism involved in this hierarchical pattern of disease progression is unknown. We describe a transgenic mouse model in which overexpression of human tau P301L is restricted to EC-II. Tau pathology progresses from EC transgene-expressing neurons to neurons without detectable transgene expression, first to EC neighboring cells, followed by propagation to neurons downstream in the synaptic circuit such as the dentate gyrus, CA fields of the hippocampus, and cingulate cortex. Human tau protein spreads to these regions and co-aggregates with endogenous mouse tau. With age, synaptic degeneration occurs in the entorhinal target zone and EC neurons are lost. These data suggest that a sequence of progressive misfolding of tau proteins, circuit-based transfer to new cell populations, and deafferentation induced degeneration are part of a process of tau-induced neurodegeneration.