Omics-based Biomarkers for the Early Alzheimer Disease Diagnosis and Reliable Therapeutic Targets Development

Background: Alzheimer’s disease (AD), the most common cause of dementia in adulthood, has great medical, social, and economic impact worldwide. Available treatments result in symptomatic relief, and most of them are indicated from the early stages of the disease. Therefore, there is an increasing body of research developing accurate and early diagnoses, as well as diseasemodifying therapies. Objective: Advancing the knowledge of AD physiopathological mechanisms, improving early diagnosis and developing effective treatments from omics-based biomarkers. Methods: Studies using omics technologies to detect early AD, were reviewed with a particular focus on the metabolites/lipids, micro-RNAs and proteins, which are identified as potential biomarkers in non-invasive samples. Results: This review summarizes recent research on metabolomics/lipidomics, epigenomics and proteomics, applied to early AD detection. Main research lines are the study of metabolites from pathways, such as lipid, amino acid and neurotransmitter metabolisms, cholesterol biosynthesis, and Krebs and urea cycles. In addition, some microRNAs and proteins (microglobulins, interleukins), related to a common network with amyloid precursor protein and tau, have been also identified as potential biomarkers. Nevertheless, the reproducibility of results among studies is not good enough and a standard methodological approach is needed in order to obtain accurate information. Conclusion: The assessment of metabolomic/lipidomic, epigenomic and proteomic changes associated with AD to identify early biomarkers in non-invasive samples from well-defined participants groups will potentially allow the advancement in the early diagnosis and improvement of therapeutic interventions.