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Research Highlight | 14 September 2018

Milk thistle extract could prevent cognitive decline in Alzheimer’s disease patients

Blocking amyloid assembly in blood vessels is a promising strategy for slowing dementia

A component of milk thistle may prevent the deterioration in brain function associated with Alzheimer’s disease by blocking the aggregation of the amyloid-β protein in the brain’s blood vessels.

Alzheimer’s disease is characterized by the accumulation of amyloid-β in both the brain’s grey matter, and the blood vessels that supply it with fuel and oxygen. Although researchers have largely focused on amyloid-β plaques and tangles in brain tissue, attention is increasingly turning to the deposits in blood vessels, which restrict the flow of blood to the brain and can trigger small clots or bleeds, damaging surrounding brain tissue. “We think they may be part of the reason for the cognitive impairment we see in Alzheimer’s disease,” says Masafumi Ihara at the National Cerebral and Cardiovascular Center in Osaka.

His team is currently investigating several molecules that may help to clear amyloid-β deposits from the brain, rather than reducing its production as with most other drugs in development for Alzheimer’s. These include cilostazol, a drug primarily used to treat leg pain, and more recently, a component of milk thistle called taxifolin: Other studies had indicated that taxifolin might inhibit the aggregation of amyloid-β and prevent it from being converted into a more toxic form through the addition of sugar molecules.

To investigate whether taxifolin could prevent amyloid-β assembly and dementia in animals, Ihara’s team fed doses daily to mice that were genetically predisposed to accumulate amyloid-β in their blood vessels as they aged. Usually, these mice would begin to show signs of dementia by 8-10 months, which can be tested by repeatedly putting them into a tank of opaque water until they learn the location of a hidden escape platform and measuring how long it takes them to find it on subsequent days. “Their behavior in the water maze showed that taxifolin completely normalized the cognitive impairment we usually see in these mice,” says Ihara. It also prevented the usual deterioration in blood flow to the brain.

Ihara’s team is now testing whether taxifolin improves symptoms in mice that have already developed dementia: “Our preliminary experiments suggest that taxifolin is partially effective at reversing cognitive impairment, even after the mice have developed it,” he says.

They are also planning a trial of taxifolin in humans with mild cognitive impairment, in collaboration with the Translational Research Informatics Center in Kobe, to see if it can slow the progression of their dementia.

References

  1. Saito, S. et al. Taxifolin inhibits amyloid-β oligomer formation and fully restores vascular integrity and memory in cerebral amyloid angiopathy. Acta Neuropathologica Communications 5. 26 (2017)| article

About the Researcher

Masafumi Ihara, Director of Neurology, National Cerebral and Cardiovascular Center Hospital

Masafumi Ihara graduated from the Kyoto University School of Medicine in 1995, and undertook clinical training, before completing a PhD in Neuroscience at the Kyoto University Graduate School of Medicine in 2003. He received his neuropathological training under the supervision of Prof. Kalaria in Newcastle University, UK, and then led a neurovascular research group as an assistant professor of the Department of Neurology in Kyoto University (2008-2012) and as a deputy director of the Department of Regenerative Medicine Research in Institute of Biomedical Research and Innovation (IBRI), Kobe (2012-2013). His research interests have focused on the pathological changes in brain blood vessels and how the alterations impact on brain health during old age.

Department of Neurology, National Cerebral and Cardiovascular Center

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