Visualization of soluble tau oligomers in TauP301L-BiFC transgenic mice demonstrates the progression of tauopathy
- Visualization of soluble tau oligomers in TauP301L-BiFC transgenic mice demonstrates the progression of tauopathy
- 배애님; 김윤경; 임성수; 류훈; 신슬기; 현승재; 김도희; 송지연; 정현정; Neil W. Kowall
- 타우; 치매; 동물모델; 생쥐; BiFC
- Issue Date
- Progress in neurobiology
- VOL 187, 101782
- Accumulation of abnormal tau aggregates in the brain is a pathological hallmark of multiple neurodegenerative disorders including Alzheimer’s disease. Increasing evidence suggests that soluble tau aggregates play a key role in tau pathology as neurotoxic species causing neuronal cell death and act as prion-like seeds mediating tau propagation. Despite the pathological relevance, there is a paucity of methods to monitor tau oligomerization in the brain. As a tool to monitor tau self-assembly in the brain, we generated a novel tau transgenic mouse, named
TauP301L-BiFC. By inroducing bimolecular fluorescence complementation technique to human tau containing a P301L mutation, we were able to monitor and quantify tau self-assembly, represented by BiFC fluorescence in the brains of transgenic TauP301L-BiFC mice. TauP301L-BiFC mice showed soluble tau oligomerization from 3 months, showing significantly enriched BiFC fluorescence in the brain. Then, massive tau fragmentation occured at 6 months showing dramatically decreased TauP301L-BiFC fluorescence. The fragmented tau species served as
a seed for insoluble tau aggregation. In a result, insoluble TauP301L-BiFC aggregates coaggregated with endogenous mouse tau accumulated in the brain, showing subsequently increased BiFC fluorescence from 9 months. Neuronal degeneration and cognitive deficits were observed from 12 months of age. TauP301L-BiFC mouse model demonstrated that methylene blue reduced the amount of soluble tau oligomers in the brain, resulting in the prevention of cognitive impairments. We assure that TauP301L-BiFC mice are a bona-fide animal tool to monitor pathological tau oligomerization in AD and other tauopathies.
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