Unbiased Metabolomic Investigation of Alzheimer's Disease Brain Points to Dysregulation of Mitochondrial Aspartate Metabolism

摘要: Alzheimer's disease (AD) is the most common cause of adult dementia. Yet complete set molecular changes accompanying this inexorable, neurodegenerative remains elusive. Here we adopted an unbiased lipidomics and metabolomics approach to surveying frozen frontal cortex samples from clinically characterized AD patients (n = 21) age-matched controls 19), revealing marked differences between them. Then, by means metabolomic pathway analysis, incorporated novel information into known biochemical pathways compared it with results a meta-analysis previously published research. We found six metabolic central metabolism as well glycerophospholipid predominantly altered in brains. Using targeted approaches MS imaging, confirmed dysregulation mitochondrial aspartate metabolism. The were further integrated clinical data, showing various degrees correlation parameters dementia pathology. Our study highlights specific, brains individuals those control subjects, emphasizing supporting future venues investigation.