BACKGROUND:
Biotin, also known as vitamin B7, is an essential dietary micronutrient that acts as a carboxylase enzyme cofactor, participating in a range of essential molecular processes ranging from gluconeogenesis and lipogenesis to amino acid metabolism and TCA cycle activity—many of which have been reported to be dysregulated in Alzheimer’s disease (AD). There is some evidence that lower levels of biotin intake are linked with increased risk of dementia and that concentrations are reduced in AD patient serum. This study aimed to ascertain whether biotin levels are similarly perturbed in the AD brain.
METHODS:
Biotin concentrations were determined in brain tissues from five regions including the motor cortex, middle temporal gyrus, cingulate gyrus, hippocampus), and sensory cortex from nine neuropathologically and clinically confirmed AD cases and nine matched controls using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Case-control differences were determined by multiple Mann-Whitney U tests with 10% FDR correction and any potential confounding effects from variables such as age, sex, tau Braak stage, etc., were determined by multiple linear regression.
RESULTS:
Biotin levels were decreased in AD cases in every investigated region, with an average decrease of ~40%. Multiple linear regression showed an effect of post-mortem delay and brain weight on biotin concentrations in the motor cortex, suggesting potential confounding effects within this region; however, no confounding effects were observed in any other brain region.
CONCLUSION:
Biotin levels appear to be diminished across the AD brain. These changes may contribute to downstream metabolic disturbances observed in AD such as altered TCA cycle activity and glucose metabolism in conjunction with other metabolic alterations which show the same pattern of dysregulation in the AD brain, such as those previously reported in pantothenic acid, TCA cycle components, and metabolites involved in glucose metabolism.