DOI: 10.1002/alz.042762
DRUG DEVELOPMENT
PODIUM PRESENTATIONS
Preclinical small-molecule drug discovery
Taxifolin is a novel therapeutic agent for Alzheimer’s disease
and cerebral amyloid angiopathy
Satoshi Saito1,2
Masashi Tanaka3
Roy O. Weller1
Masafumi Ihara2
Noriko Satoh-Asahara4
Roxana O. Carare1
1
University of Southampton, Southampton,
United Kingdom
2
National Cerebral and Cardiovascular
Center, Osaka, Japan
3
Health Science University, Yamanashi, Japan
4
National Hospital Organization Kyoto
Medical Center, Kyoto, Japan
Abstract
Background: Impaired amyloid-β clearance from brain along intramural periarterial
drainage (IPAD) is key in the pathogenesis of Alzheimer’s disease (AD). Facilitating
IPAD would delay or prevent cerebral amyloid angiopathy (CAA). Taxifolin, a flavonol
with strong anti-oxidative and anti-glycation activities, has been reported to disassemble amyloid-β. Here, we test the hypothesis that taxifolin has therapeutic potential in
Correspondence
Satoshi Saito, University of Southampton,
Southampton, United Kingdom.
Email: satoshi.saito@soton.ac.uk
reducing AD and CAA.
Method: Tg-SwDI mice, as a model of AD and CAA, were treated with either taxifolin
or vehicle alone from the age of one month. Wild type and Tg-SwDI mice aged eight
to thirteen months were used for the investigation of the amyloid-β metabolism in
vivo, amyloid-β pathology, cerebral blood flow, cerebrovascular reactivity and cognitive function. Cerebral blood flow and cerebrovascular reactivity were evaluated by
using laser speckle flowmetry. Cognitive function was assessed by Morris water maze.
Thioflavin-T fluorescence assay and transmission electron microscope were to examine the effect of taxifolin on amyloid-β disaggregation.
Result: There was reduced accumulation of amyloid-β in the cerebrovasculature in
the hippocampus in taxifolin-treated Tg-SwDI mice compared to the mice treated with
vehicle alone (n = 5). Tg-SwDI mice treated with taxifolin exhibited decreased expression of amyloid-β precursor protein in the hippocampus, suppressed oligomerization
of amyloid-β in the brain and increased levels of amyloid-β40 in the blood (n = 4-6).
Taxifolin completely restored the cerebral blood flow and cerebrovascular reactivity in
Tg-SwDI mice (n = 4-6). Spatial reference memory returned to normal levels following
treatment with taxifolin (n = 10-17). Amyloid-β aggregation was suppressed by taxifolin treatment in vitro.
Conclusion: Taxifolin prevents overproduction and oligomerization of amyloid-β and
facilitates its clearance into the blood. Taxifolin thus appears to be a promising therapeutic agent for AD and CAA.
Alzheimer’s Dement. 2020;16(Suppl. 9):e042762.
https://doi.org/10.1002/alz.042762
wileyonlinelibrary.com/journal/alz
© 2020 the Alzheimer’s Association
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