Shin, Seulgi Kim, Dohee Song, Ji Yeon Jeong, Hyeanjeong Hyeon, Seung Jae Kowall, Neil W. Ryu, Hoon Pae, Ae Nim Lim, Sungsu Kim, Yun Kyung 2024-01-19T18:00:47Z 2024-01-19T18:00:47Z 2021-09-05 2020-04 0301-0082 https://pubs.kist.re.kr/handle/201004/118804 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 introducing 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. English Pergamon Press Ltd. Visualization of soluble tau oligomers in TauP301L-BiFC transgenic mice demonstrates the progression of tauopathy Article 10.1016/j.pneurobio.2020.101782 1 Progress in Neurobiology, v.187 Progress in Neurobiology 187 Y scie scopus 000525929700004 2-s2.0-85080134639 Neurosciences Neurosciences & Neurology Review ALZHEIMERS-DISEASE METHYLENE-BLUE FILAMENT FORMATION INTRACELLULAR TAU AXONAL-TRANSPORT MOUSE MODEL IN-VITRO PHOSPHORYLATION AGGREGATION BRAIN Tau P301L BiFC Tau transgenic mouse Tau oligomer Tauopathy