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Publication : Thioflavin-positive tau aggregates complicating quantification of amyloid plaques in the brain of 5XFAD transgenic mouse model.

First Author  Shin J Year  2021
Journal  Sci Rep Volume  11
Issue  1 Pages  1617
PubMed ID  33452414 Mgi Jnum  J:300382
Mgi Id  MGI:6502216 Doi  10.1038/s41598-021-81304-6
Citation  Shin J, et al. (2021) Thioflavin-positive tau aggregates complicating quantification of amyloid plaques in the brain of 5XFAD transgenic mouse model. Sci Rep 11(1):1617
abstractText  Transgenic mouse models recapitulating Alzheimer's disease (AD) pathology are pivotal in molecular studies and drug evaluation. In transgenic models selectively expressing amyloid-beta (Abeta), thioflavin S (ThS), a fluorescent dye with beta-sheet binding properties, is widely employed to observe amyloid plaque accumulation. In this study, we investigated the possibility that a commonly used Abeta-expressing AD model mouse, 5XFAD, generates ThS-positive aggregates of beta-sheet structures in addition to Abeta fibrils. To test this hypothesis, brain sections of male and female 5XFAD mice were double-stained with ThS and monoclonal antibodies against Abeta, tau, or alpha-synuclein, all of which aggregates are detected by ThS. Our results revealed that, in addition to amyloid plaques, 5XFAD mice express ThS-positive phospho-tau (p-tau) aggregates. Upon administration of a small molecule that exclusively disaggregates Abeta to 5XFAD mice for six weeks, we found that the reduction level of plaques was smaller in brain sections stained by ThS compared to an anti-Abeta antibody. Our findings implicate that the use of ThS complicates the quantification of amyloid plaques and the assessment of Abeta-targeting drugs in 5XFAD mice.
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