The metabolomic and proteomic basis of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD/MCI pathogenesis is unclear. This study compared the metabolomic and proteomic signature of plasma from cognitively normal (CN) and dementia patients diagnosed with MCI or AD, to identify specific cellular pathways and new biomarkers altered with the progression of the disease. We analysed 80 plasma samples from individuals with MCI or AD, as well as age- and gender-matched CN individuals, by utilising mass spectrometry methods and data analyses that included combined pathway analysis and model predictions. Several proteins clearly identified AD from the MCI and CN groups and included plasma actins, mannan-binding lectin serine protease 1, serum amyloid A2, fibronectin and extracellular matrix protein 1 and Keratin 9. The integrated pathway analysis showed various metabolic pathways were affected in AD, such as the arginine, alanine, aspartate, glutamate and pyruvate metabolism pathways. Therefore, our multi-omics approach identified novel plasma biomarkers for the MCI and AD groups, identified changes in metabolic processes, and may form the basis of a biomarker panel for stratifying dementia participants in future clinical trials.
Keywords: Alzheimer’s disease; biomarkers; metabolomics; proteomics; systems biology.