Recent Updates on Lipid Landscapes in Neonatal and Adult Neurological Disorders: Advancing Mass Spectrometry and Lipidomics for Disease Insight: A Systematic Review

The brain's complexity arises from intricate neural circuitry and dynamic molecular interactions. While genomics and proteomics have expanded understanding of brain pathology, lipidomics- particularly through metabolite and membrane lipid profiling-has emerged as a critical tool for elucidating phenotype-specific molecular mechanisms, especially those underlying neurodevelopmental and neurodegenerative disorders. Given the brain's high lipid content and the role of bioactive lipids in neural function, a deeper understanding of age-specific lipidomic landscapes is essential. Methods: A comprehensive literature review was conducted using scientific databases such as PubMed, Scopus, and Web of Science. Key search terms included "lipidomics," "brain development," "neurodegeneration," "mass spectrometry," "neonatal brain," and "adult brain." Studies that applied advanced mass spectrometry techniques for brain lipid profiling, including LC-MS and GC-MS, were prioritized. The review focused on the identification, function, and clinical relevance of lipid species across age groups and neurological conditions. Results: Distinct lipidomic profiles were observed between neonatal and adult brains. Neonatal brains were enriched in DHA-containing phospholipids, which are critical for synaptogenesis and neuronal growth. In adult brains, lipids such as sphingolipids and cholesterol showed higher abundance and functional diversity, contributing to membrane integrity, signal transduction, and neuroprotection. Alterations in lipid metabolism were linked to various neurological disorders, notably multiple sclerosis, Alzheimer's disease, and Parkinson's disease. The review also identified challenges in lipidomics data integration, standardization, and its application to clinical diagnostics. Discussion: The findings highlight the critical importance of lipidomics in understanding brain development and neurodegeneration. Age-specific lipid signatures not only provide insights into the molecular basis of neurological disorders but also offer promising avenues for early diagnosis and therapeutic targeting. Despite advances in mass spectrometry and data analysis, challenges remain in integrating lipidomic data with other omics layers, necessitating further methodological and computational developments. Ultimately, lipidomics represents a transformative approach to decoding brain biology across the lifespan. Conclusion: This review elucidates the pivotal role of lipidomics in revealing age-specific molecular signatures in the brain, with clear distinctions between neonatal and adult lipid profiles. In neonatal brains, DHA-enriched phospholipids are fundamental for neurodevelopmental processes such as synaptogenesis and myelination, whereas in adult brains lipid networks are more complex, supporting neuronal maintenance, signaling, and neuroprotection. Dysregulation of these lipid pathways is closely associated with the pathophysiology of neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease, and Parkinson's disease. Advanced mass spectrometry technologies have facilitated high-resolution lipid profiling, enabling the identification of potential biomarkers and therapeutic targets. The broader implications of these findings are that lipidomics, when integrated with multi-omics approaches, can significantly enhance understanding of brain function and disease across the lifespan, ultimately informing the development of personalized diagnostic tools and age-specific therapeutic strategies for neurological disorders.