Omics Data and Their Integrative Analysis to Support Stratified Medicine in Neurodegenerative Diseases

Abstract

Molecular and clinical heterogeneity is increasingly recognized as a common characteristic of neurodegenerative diseases (NDs), such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. This heterogeneity makes difficult the development of early diagnosis and effective treatment approaches, as well as the design and testing of new drugs. As such, the stratification of patients into meaningful disease subgroups, with clinical and biological relevance, may improve disease management and the development of effective treatments. To this end, omics technologies—such as genomics, transcriptomics, proteomics and metabolomics—are contributing to offer a more comprehensive view of molecular pathways underlying the development of NDs, helping to differentiate subtypes of patients based on their specific molecular signatures. In this article, we discuss how omics technologies and their integration have provided new insights into the molecular heterogeneity underlying the most prevalent NDs, aiding to define early diagnosis and progression markers as well as therapeutic targets that can translate into stratified treatment approaches, bringing us closer to the goal of personalized medicine in neurology.

Deregulation of ncRNA in Neurodegenerative Disease: Focus on circRNA, lncRNA and miRNA in Amyotrophic Lateral Sclerosis

“…Other studies have been conducted on SALS post-mortem cortex samples and allowing distinctions into molecular subtypes characterized by different combinations of genes and pathways deregulated ( La Cognata et al, 2021 ). The existence of distinct molecular subtypes of ALS have also been highlighted in other works ( Aronica et al, 2015 ).…”

Biomarkers of Neurodegenerative Diseases: Biology, Taxonomy, Clinical Relevance, and Current Research Status

“…Multi-omics analyses and characterizations of patients’ omics profiles allow deeper examinations of neurodegenerative diseases, providing a more comprehensive perspective of multifactorial disorders that supports the development of specific targeted and personalized therapies [ 40 ]. If they meet conditions of reproducibility and easy repeatability, they identify the ideal biomarkers for measuring disease progression and for monitoring responses to disease-modifying therapies [ 41 ].…”

Dysregulated miRNAs as Biomarkers and Therapeutical Targets in Neurodegenerative Diseases

“…Although the molecular mechanisms underlying PD are not fully elucidated, the progressive deterioration of vulnerable DNs arises from several cellular disturbances, including protein misfolding and aggregation, synaptic damages, apoptosis, mitochondrial dysfunctions, oxidative stress, impairment of the UPS, and neuroinflammation [ 102 ].…”