Multi-Omics, an Integrated Approach to Identify Novel Blood Biomarkers of Alzheimer's Disease

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.

Automated summary

The metabolomic and proteomic basis of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is not well understood. This study examined the plasma samples of individuals with MCI or AD, as well as age- and gender-matched cognitively normal individuals, to identify cellular pathways and biomarkers associated with the diseases. The analysis revealed specific proteins that distinguish AD from MCI and cognitively normal groups, and identified various metabolic pathways affected in AD. These findings contribute to the understanding of the diseases and may be useful for future clinical trials.