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Abstract

Multipath Natural Product Supplement Suppresses Dementia Symptoms in Amyloid-β and Tau Transgenic Drosophila

Background: Numerous reports on Alzheimer’s Disease (AD) indicate that AD has many biochemical pathways. However, most AD treatments have targeted a single pathway such as beta amyloid or phosphorylated tau and have not been very successful in stopping AD progression. To address the multipath nature of AD, we have used multiple natural products that target critical aging and independent AD pathways to test whether a multipath approach might be more effective than the single pathway approaches typically used.

Methods and findings: We have constructed Drosophila melanogaster models of AD with inducible transgenic human Amyloid-β and tau mutations. Induction of either AD mutant gene in the transgenic flies after emergence from pupal stage leads to the early onset of slowed mobility that was tracked by assaying crawl times as a function of age. The transgenic Amyloid-β and tau Drosophila assays were utilized to test various natural products that target separate biological pathways involved in brain aging and dementia. Screening a library of natural products, we identified a group of 7 natural substances (MX100A) that synergistically prevented nearly all early mobility difficulties and reverses the lifeshortening effects of Amyloid-β and tau. The favorable results on AD symptoms in Drosophila with MX100A were observed in animals treated from youth and from later adult ages. MX100A had no observed negative side effects.

Conclusion: Treatment of transgenic AD Drosophila with the multipath MX100A dietary supplement prevents nearly all early mobility difficulties and reverses the lifeshortening effects of Amyloid-β and tau. In patients with AD, progressively more severe mobility difficulties and heightened risks of mortality are common symptoms of the later stages of AD. While successful animal results have not typically translated into effective treatments for AD, the multipath MX100A treatment results are promising enough to warrant further testing.


Author(s): Kennedy Matsagas, Cristina Rizza, Ben Goertzel, Gregory Benford and Bryant Villeponteau

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