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

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

Author information

1
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, 3010, Australia.
2
The Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, VIC, 3010, Australia.
3
Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
4
The Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Parkville, VIC, 3010, Australia.
5
The Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3083, Australia.
6
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, 3010, Australia. kbarnham@unimelb.edu.au.
7
The Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, VIC, 3010, Australia. kbarnham@unimelb.edu.au.

Abstract

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

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