This is a summary of a very interesting publication, with the same title as above, by Takayuki Inoue (Kyoto Medical Center), Satoshi Saito, Masashi Tanaka and edited by Lawrence Steinman (Stanford University School of Medicine).

It was published April 29, 2019 in the Proceedings of the National Academy of Sciences (PNAS) 116 (20) 10031-10038
Here is a link: https://doi.org/10.1073/pnas.1901659116

Editors’ notes:
1. This research highlights the considerable potential of taxifolin in protecting against cerebral amyloid angiopathy. However, the article points out that more research is needed to determine the “optimal dose, timing, and duration” of taxifolin administration. This caution is especially relevant since taxifolin is readily available without prescription, and there could be side effects.

2. This summary was prepared with much assistance by ChatGPT, which means that it should be checked for accuracy before relying on

This study demonstrates that taxifolin, despite its limited ability to cross the blood-brain barrier (BBB), has several beneficial effects when administered orally over several months in a mouse model of Cerebral Amyloid Angiopathy (CAA). Taxifolin treatment reduces the accumulation of amyloid-β, suppresses microglial activation, inhibits oxidative tissue damage, and may contribute to lymphangiogenesis [formation of new lymphatic vessels] in the brain…potentially preventing CAA development and maintaining cognitive function.

Taxifolin appears to lower amyloid-β levels in the brain, possibly by stimulating the IPAD system [intramural periarterial drainage] and suppressing the ApoE–ERK1/2–APP axis responsible for amyloid-β production. Despite limited BBB permeability, taxifolin exhibits these actions effectively in vivo…”

Additionally, taxifolin promotes the expression of lymphangiogenic factors LYVE-1 and VEGF-D, which may positively impact cognitive function and lymphatic vasculature integrity. These effects could be related to taxifolin’s interaction with estrogen receptor signaling in the brain.

Elevated TREM2 expression is associated with inflammation, which can accelerate CAA progression. Taxifolin treatment improves the activation profiles of proinflammatory responses, including TREM2 expression, suggesting that TREM2-expressing microglia may be a key target for CAA treatment.

Taxifolin also reduces glutamate levels and oxidative tissue damage, benefiting other types of microglia with lower TREM2 expression. Combining taxifolin with omega-3 polyunsaturated fatty acids (PUFAs) may offer synergistic neuroprotective effects.

The mechanisms behind taxifolin’s effects on microglial phenotypes and DNA methylation require further investigation. Clinical studies are needed to determine the optimal dose, timing, and duration of taxifolin administration for CAA prevention and to assess its therapeutic effects on established CAA in humans.

In summary, this study highlights the potential of taxifolin as a preventive treatment for CAA, with promising effects on amyloid-β reduction, microglial modulation, and oxidative damage in the brain…