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

Leah C. Beauchamp, Jacky Chan, Lin W. Hung, Benjamin S. Padman, Laura J. Vella, Xiang M. Liu, Bradley Coleman, Ashley I. Bush, Michael Lazarou, Andrew F. Hill, Laura Jacobson, Kevin J. Barnham

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article number57
Number of pages12
JournalActa neuropathologica communications
Volume6
Issue number1
DOIs
Publication statusPublished - 5 Jul 2018

Keywords

  • Autophagy
  • Neurodegeneration
  • Olfaction
  • Parkinson’s disease
  • Tau

Cite this

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. / Ablation of tau causes an olfactory deficit in a murine model of Parkinson's disease. In: Acta neuropathologica communications. 2018 ; Vol. 6, No. 1.
@article{a0ba259a9564488f9fab83fdffff954e,
title = "Ablation of tau causes an olfactory deficit in a murine model of Parkinson's disease",
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",
author = "Beauchamp, {Leah C.} and Jacky Chan and Hung, {Lin W.} and Padman, {Benjamin S.} and Vella, {Laura J.} and Liu, {Xiang M.} and Bradley Coleman and Bush, {Ashley I.} and Michael Lazarou and Hill, {Andrew F.} and Laura Jacobson and Barnham, {Kevin J.}",
year = "2018",
month = "7",
day = "5",
doi = "10.1186/s40478-018-0560-y",
language = "English",
volume = "6",
journal = "Acta neuropathologica communications",
issn = "2051-5960",
publisher = "Springer-Verlag London Ltd.",
number = "1",

}

Beauchamp, LC, Chan, J, Hung, LW, Padman, BS, Vella, LJ, Liu, XM, Coleman, B, Bush, AI, Lazarou, M, Hill, AF, Jacobson, L & Barnham, KJ 2018, 'Ablation of tau causes an olfactory deficit in a murine model of Parkinson's disease' Acta neuropathologica communications, vol. 6, no. 1, 57. https://doi.org/10.1186/s40478-018-0560-y

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

In: Acta neuropathologica communications, Vol. 6, No. 1, 57, 05.07.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Ablation of tau causes an olfactory deficit in a murine model of Parkinson's disease

AU - Beauchamp, Leah C.

AU - Chan, Jacky

AU - Hung, Lin W.

AU - Padman, Benjamin S.

AU - Vella, Laura J.

AU - Liu, Xiang M.

AU - Coleman, Bradley

AU - Bush, Ashley I.

AU - Lazarou, Michael

AU - Hill, Andrew F.

AU - Jacobson, Laura

AU - Barnham, Kevin J.

PY - 2018/7/5

Y1 - 2018/7/5

N2 - 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.

AB - 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.

KW - Autophagy

KW - Neurodegeneration

KW - Olfaction

KW - Parkinson’s disease

KW - Tau

UR - http://www.scopus.com/inward/record.url?scp=85062044963&partnerID=8YFLogxK

U2 - 10.1186/s40478-018-0560-y

DO - 10.1186/s40478-018-0560-y

M3 - Article

VL - 6

JO - Acta neuropathologica communications

JF - Acta neuropathologica communications

SN - 2051-5960

IS - 1

M1 - 57

ER -