Publication Type Academic Article
Authors Vidoni E, Choi I, Lee P, Reed G, Zhang N, Pleen J, Mahnken J, Clutton J, Becker A, Sherry E, Bothwell R, Anderson H, Harris R, Brooks W, Wilkins H, Mosconi L, Burns J, Swerdlow R
Journal Alzheimers Dement
Volume 17
Issue 1
Pagination 7-17
Date Published 07/27/2020
ISSN 1552-5279
Keywords Alzheimer Disease, Oxaloacetic Acid
Abstract INTRODUCTION: Brain bioenergetics are defective in Alzheimer's disease (AD). Preclinical studies find oxaloacetate (OAA) enhances bioenergetics, but human safety and target engagement data are lacking. METHODS: We orally administered 500 or 1000 mg OAA, twice daily for 1 month, to AD participants (n = 15 each group) and monitored safety and tolerability. To assess brain metabolism engagement, we performed fluorodeoxyglucose positron emission tomography (FDG PET) and magnetic resonance spectroscopy before and after the intervention. We also assessed pharmacokinetics and cognitive performance. RESULTS: Both doses were safe and tolerated. Compared to the lower dose, the higher dose benefited FDG PET glucose uptake across multiple brain regions (P < .05), and the higher dose increased parietal and frontoparietal glutathione (P < .05). We did not demonstrate consistent blood level changes and cognitive scores did not improve. CONCLUSIONS: 1000 mg OAA, taken twice daily for 1 month, is safe in AD patients and engages brain energy metabolism.
DOI 10.1002/alz.12156
PubMed ID 32715609
PubMed Central ID PMC8084114
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