期刊
SCIENTIFIC REPORTS
卷 11, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41598-021-81304-6
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资金
- Korea Health Industry Development Institute (KHIDI) [HI18C0836]
- National Research Foundation of Korea [NRF-2018R1A6A1A03023718, NRF-2018M3C7A1021858]
- POSCO TJ Foundation (POSCO Science Fellowship)
- National Research Foundation of Korea [2018M3C7A1021858] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
This study revealed the presence of ThS-positive phospho-tau (p-tau) aggregates in addition to amyloid plaques in the brains of 5XFAD mice. The use of ThS complicates the quantification of amyloid plaques and may hinder the assessment of A beta-targeting drugs in 5XFAD mice.
Transgenic mouse models recapitulating Alzheimer's disease (AD) pathology are pivotal in molecular studies and drug evaluation. In transgenic models selectively expressing amyloid-beta (A beta), 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 A beta -expressing AD model mouse, 5XFAD, generates ThS-positive aggregates of beta -sheet structures in addition to A beta fibrils. To test this hypothesis, brain sections of male and female 5XFAD mice were double-stained with ThS and monoclonal antibodies against A beta, 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 A beta 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-A beta antibody. Our findings implicate that the use of ThS complicates the quantification of amyloid plaques and the assessment of A beta -targeting drugs in 5XFAD mice.
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