Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform

Neuron. 1999 Nov;24(3):751-62. doi: 10.1016/s0896-6273(00)81127-7.


Filamentous tau aggregates are hallmarks of tauopathies, e.g., frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) and amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC). Since FTDP-17 tau gene mutations alter levels/functions of tau, we overexpressed the smallest human tau isoform in the CNS of transgenic (Tg) mice to model tauopathies. These mice acquired age-dependent CNS pathology similarto FTDP-17 and ALS/PDC, including insoluble, hyperphosphorylated tau and argyrophilic intraneuronal inclusions formed by tau-immunoreactive filaments. Inclusions were present in cortical and brainstem neurons but were most abundant in spinal cord neurons, where they were associated with axon degeneration, diminished microtubules (MTs), and reduced axonal transport in ventral roots, as well as spinal cord gliosis and motor weakness. These Tg mice recapitulate key features of tauopathies and provide models for elucidating mechanisms underlying diverse tauopathies, including Alzheimer's disease (AD).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / physiology*
  • Animals
  • Axonal Transport / physiology
  • Axons / pathology
  • Brain / metabolism
  • Brain / pathology
  • Central Nervous System Diseases / etiology*
  • Central Nervous System Diseases / metabolism*
  • Central Nervous System Diseases / pathology
  • Disease Progression
  • Gliosis / genetics
  • Humans
  • Inclusion Bodies / ultrastructure
  • Mice
  • Mice, Transgenic / genetics
  • Muscle Weakness / genetics
  • Nerve Degeneration / pathology
  • Phosphorylation
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Isoforms / physiology
  • Protein Structure, Secondary
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • tau Proteins / chemistry
  • tau Proteins / genetics
  • tau Proteins / metabolism
  • tau Proteins / physiology*


  • Protein Isoforms
  • tau Proteins