Ablation of tau causes an olfactory deficit in a murine model of Parkinson's disease

Acta Neuropathol Commun. 2018 Jul 5;6(1):57. doi: 10.1186/s40478-018-0560-y.


Parkinson's disease is diagnosed upon the presentation of motor symptoms, resulting from substantial degeneration of dopaminergic neurons in the midbrain. Prior to diagnosis, there is a lengthy prodromal stage in which non-motor symptoms, including olfactory deficits (hyposmia), develop. There is limited information about non-motor impairments and there is a need for directed research into these early pathogenic cellular pathways that precede extensive dopaminergic death in the midbrain. The protein tau has been identified as a genetic risk factor in the development of sporadic PD. Tau knockout mice have been reported as an age-dependent model of PD, and this study has demonstrated that they develop motor deficits at 15-months-old. We have shown that at 7-month-old tau knockout mice present with an overt hyposmic phenotype. This olfactory deficit correlates with an accumulation of α-synuclein, as well as autophagic impairment, in the olfactory bulb. This pathological feature becomes apparent in the striatum and substantia nigra of 15-month-old tau knockout mice, suggesting the potential for a spread of disease. Initial primary cell culture experiments have demonstrated that ablation of tau results in the release of α-synuclein enriched exosomes, providing a potential mechanism for disease spread. These alterations in α-synuclein level as well as a marked autophagy impairment in the tau knockout primary cells recapitulate results seen in the animal model. These data implicate a pathological role for tau in early Parkinson's disease.

Keywords: Autophagy; Neurodegeneration; Olfaction; Parkinson’s disease; Tau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Autophagy
  • Brain / metabolism
  • Brain / pathology
  • Disease Models, Animal
  • Exosomes / metabolism
  • Exosomes / pathology
  • Exosomes / ultrastructure
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron, Transmission
  • Neurons / metabolism
  • Neurons / pathology
  • Neurons / ultrastructure
  • Odorants
  • Olfaction Disorders / etiology*
  • Olfaction Disorders / genetics*
  • Olfactory Bulb / metabolism
  • Olfactory Bulb / pathology
  • Parkinson Disease / complications*
  • Parkinson Disease / pathology
  • Psychomotor Performance / physiology
  • Sequestosome-1 Protein / metabolism
  • alpha-Synuclein / metabolism
  • tau Proteins / deficiency*
  • tau Proteins / genetics


  • Sequestosome-1 Protein
  • Sqstm1 protein, mouse
  • alpha-Synuclein
  • tau Proteins