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

TitlePropagation of tau pathology in a model of early Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2012
Authorsde Calignon, A, Polydoro, M, Suárez-Calvet, M, William, C, Adamowicz, DH, Kopeikina, KJ, Pitstick, R, Sahara, N, Ashe, KH, Carlson, GA, Spires-Jones, TL, Hyman, BT
JournalNeuron
Volume73
Issue4
Pagination685-97
Date Published2012 Feb 23
ISSN1097-4199
KeywordsAge Factors, Alzheimer Disease, Animals, Disease Models, Animal, Disease Progression, Entorhinal Cortex, Epitopes, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Gliosis, Hippocampus, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Nerve Degeneration, Neurofibrillary Tangles, Neurons, RNA, Messenger, Serine, tau Proteins, Tauopathies
Abstract

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.

DOI10.1016/j.neuron.2011.11.033
Alternate JournalNeuron
PubMed ID22365544
PubMed Central IDPMC3292759
Grant ListAG026249 / AG / NIA NIH HHS / United States
AG08487 / AG / NIA NIH HHS / United States
K08 NS069811 / NS / NINDS NIH HHS / United States
K08NS069811 / NS / NINDS NIH HHS / United States
K99AG33670 / AG / NIA NIH HHS / United States
R00 AG033670 / AG / NIA NIH HHS / United States
R01 AG008487 / AG / NIA NIH HHS / United States
R01 AG008487-20 / AG / NIA NIH HHS / United States
R01 AG026249 / AG / NIA NIH HHS / United States
R01 AG026249-08 / AG / NIA NIH HHS / United States
R21 AG038835 / AG / NIA NIH HHS / United States
R21 AG038835-01A1 / AG / NIA NIH HHS / United States
R21 AG038835-02 / AG / NIA NIH HHS / United States
R21 NS067127 / NS / NINDS NIH HHS / United States
R21AG038835-01A1 / AG / NIA NIH HHS / United States
Top50 Topics: 
Tau, Pathology
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Source URL: https://www.j-alz.com/content/propagation-tau-pathology-model-early-alzheimers-disease?page=0