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

• Published in: Acta neuropathologica communications Vol. 6; no. 1; p. 57
• Main Authors: Beauchamp, Leah C, Chan, Jacky, Hung, Lin W, Padman, Benjamin S, Vella, Laura J, Liu, Xiang M, Coleman, Bradley, Bush, Ashley I, Lazarou, Michael, Hill, Andrew F, Jacobson, Laura, Barnham, Kevin J
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 05.07.2018; BioMed Central; BMC
• Subjects: Age; Age Factors; alpha-Synuclein - metabolism; Animals; Autophagy; Brain - metabolism; Brain - pathology; Brain research; Disease Models, Animal; Dopamine; Exosomes - metabolism; Exosomes - pathology; Exosomes - ultrastructure; Genotype & phenotype; Mice; Mice, Transgenic; Microscopy, Electron, Transmission; Neurodegeneration; Neurons - metabolism; Neurons - pathology; Neurons - ultrastructure; Neuropathology; Odorants; Olfaction; Olfaction Disorders - etiology; Olfaction Disorders - genetics; Olfactory Bulb - metabolism; Olfactory Bulb - pathology; Parkinson Disease - complications; Parkinson Disease - pathology; Parkinson's disease; Pathogenesis; Pathology; Proteins; Psychomotor Performance - physiology; Sequestosome-1 Protein - metabolism; Tau; tau Proteins - deficiency; tau Proteins - genetics; Transgenic animals; Tau; Neurodegeneration; Autophagy; Parkinson’s disease; Olfaction
• ISSN: 2051-5960; 2051-5960
• 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.