Cairns, Nigel J

Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Propagation of tau pathology in a model of early Alzheimer's disease.

Alix de Calignon; Manuela Polydoro; Marc Suárez-Calvet; Christopher William; David H Adamowicz; Kathy J Kopeikina; Rose Pitstick; Naruhiko Sahara; Karen H Ashe; George A Carlson; et al. (Profiled Author: Hyman, Bradley T)

MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Alzheimer's Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Neuron 2012;73(4):685-97.

Neurofibrillary tangles advance from layer II of the entorhinal cortex (EC-II) toward limbic and association cortices as Alzheimer's disease 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 coaggregates 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.

4 Originating Grant

• 1.

  HYMAN, BRADLEY T

  A Model of Early Alzheimer Disease

  1 April 2011 - 31 March 2013

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 392,821

• 2.

  HYMAN, BRADLEY T.

  Anatomical Changes in Tau Transgenic Models

  30 September 2004 - 31 August 2015

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 2,379,623

• 3.

  HYMAN, BRADLEY T

  PATHOLOGICAL ALTERATIONS IN ALZHEIMER'S DISEASE

  1 August 1989 - 30 November 1994

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 554,426

• 4.

  HYMAN, BRADLEY T

  Neurologic Alterations in Alzheimer's Disease

  1 August 1989 - 31 August 2011

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 7,608,351

Scientific Context

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