Objective: To examine the distribution of a novel tau pathology and its interaction with alpha-synuclein in two mouse model of Parkinson’s disease (PD).

Background: Cleavage of tau by asparagine endopeptidase (AEP) is a newly discovered tau pathology mediating the neurofibrillary pathology in Alzheimer’s disease. Tau fragment 1-368, cleavaged by AEP at N368, has been shown to aggregate and strongly trigger neurodegeneration.

Methods: Two mouse model of PD were evaluated. 1 mg/kg rotenone once a day for 40 d and 25mg/kg MPTP twice a week were given subcutaneously to induce PD models respectively. Rotarod test and pole test were used to assess locomotor activity. Western blot was conducted to evaluate levels of tau fragment 1-368 and alpha-synuclein ser129 in substantia nigra,striatum and hippocampus. Immunohistochemical staining was used to explore tau fragment 1-368 and alpha-synuclein ser129 expression. Double-immunofluorescence was performed to examine the co-localization of tau fragment 1-368 and alpa-synuclein.

Results: The two models displayed worse locomotor activity in Rotarod test and pole test. Western blot analyses displayed a significant increase of tau fragment 1-368 and alpha-synuclein ser129 in striatum and substantia nigra, while there was no evidence of changes in hippocampus. The same results was obtained by immunohistochemical staining. And ascended cellular co-localization of tau fragment 1-368 and alpha-synuclein was discovered by immunofluorescence microscopy, which was more obvious in the striatum.

Conclusions: Tau fragment 1-368 levels was increased in the striatum and substantia nigra of two models and co-localized with alpha-synuclein, especially in the striatum, indicating activated AEP may also play a role in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/increased-cellular-co-localization-of-tau-fragment-1-368-and-alpha-synuclein-in-two-mouse-model-of-parkinsons-disease/