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Tau suppression in a neurodegenerative mouse model improves memory function.

Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in the brains of patients with neurodegenerative diseases and have been implicated in mediating neuronal death and cognitive deficits. Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, neuronal loss, and behavioral impairments. After the suppression of transgenic tau, memory function recovered, and neuron numbers stabilized, but to our surprise, NFTs continued to accumulate. Thus, NFTs are not sufficient to cause cognitive decline or neuronal death in this model of tauopathy.

Pubmed ID: 16020737


  • Santacruz K
  • Lewis J
  • Spires T
  • Paulson J
  • Kotilinek L
  • Ingelsson M
  • Guimaraes A
  • DeTure M
  • Ramsden M
  • McGowan E
  • Forster C
  • Yue M
  • Orne J
  • Janus C
  • Mariash A
  • Kuskowski M
  • Hyman B
  • Hutton M
  • Ashe KH


Science (New York, N.Y.)

Publication Data

July 15, 2005

Associated Grants

  • Agency: NIA NIH HHS, Id: P01 AG015453
  • Agency: NIA NIH HHS, Id: P01-AG15453
  • Agency: NIA NIH HHS, Id: R01 AG008487
  • Agency: NIA NIH HHS, Id: R01 AG026249
  • Agency: NIA NIH HHS, Id: R01 AG026252
  • Agency: NINDS NIH HHS, Id: R01 NS033249
  • Agency: NINDS NIH HHS, Id: R01 NS046355
  • Agency: PHS HHS, Id: R01-026252
  • Agency: NIA NIH HHS, Id: R01-AG08487
  • Agency: NIA NIH HHS, Id: R01-AG26249
  • Agency: NINDS NIH HHS, Id: R01-NS46355
  • Agency: NIA NIH HHS, Id: T31-AG00277

Mesh Terms

  • Aging
  • Animals
  • Atrophy
  • Brain
  • Cognition
  • Disease Progression
  • Doxycycline
  • Hippocampus
  • Humans
  • Maze Learning
  • Memory
  • Mice
  • Mice, Transgenic
  • Neurodegenerative Diseases
  • Neurofibrillary Tangles
  • Neuronal Plasticity
  • Neurons
  • Organ Size
  • Phosphorylation
  • RNA, Messenger
  • Solubility
  • tau Proteins