Ablation of tau causes an olfactory deficit in a murine model of Parkinson's disease.
Leah C BeauchampJacky ChanLin W HungBenjamin S PadmanLaura J VellaXiang M LiuBradley ColemanAshley I BushMichael LazarouAndrew F HillLaura JacobsonKevin J BarnhamPublished in: Acta neuropathologica communications (2018)
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.
Keyphrases
- cerebrospinal fluid
- traumatic brain injury
- cell death
- risk factors
- stem cells
- healthcare
- oxidative stress
- mesenchymal stem cells
- signaling pathway
- computed tomography
- small molecule
- magnetic resonance imaging
- endoplasmic reticulum stress
- parkinson disease
- binding protein
- health information
- genome wide
- atrial fibrillation
- contrast enhanced
- amino acid
- pi k akt
- diffusion weighted imaging