Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 59, Issue 1, Pages 291-300Publisher
IOS PRESS
DOI: 10.3233/JAD-170077
Keywords
Alzheimer's disease; biomarker; cytochrome oxidase; mitochondria; S-equol
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Funding
- Ausio Pharmaceuticals, LLC
- University of Kansas Alzheimer's Disease Center [P30AG035982]
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Reductions in bioenergetic fluxes, mitochondrial enzyme activities, and mitochondrial number are observed in Alzheimer's disease (AD). Preclinical work indicates estrogen pathway signaling by either estrogen or selective beta estrogen receptor (ER beta) agonists benefits these parameters. To assess whether an ER beta agonist could improve mitochondrial function in actual AD subjects, we administered S-equol (10 mg twice daily) to 15 women with AD and determined the platelet mitochondria cytochrome oxidase (COX) activity before initiating S-equol (lead-in), after two weeks of S-equol (active treatment), and two weeks after stopping S-equol (wash-out). Because the intra-individual variation of this enzyme across samples taken at different times was unknown we used a nonparametric, single-arm, dichotomous endpoint that classified subjects whose active treatment COX activity exceeded the average of their lead-in and wash-out measures as positive responders. Eleven positive responses were observed (p < 0.06). The implications of this finding on our null hypothesis (that S-equol does not influence platelet mitochondria COX activity) are discussed. To our knowledge, this is the first time a direct mitochondrial target engagement biomarker has been utilized in an AD clinical study.
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