(Triggering receptor expressed on myeloid cells 2) genes, further makes lipid transport and lipid-sensing pathways central to late-onset AD vulnerability. Recent developments in lipidomics based on mass spectrometry have revealed concerted changes in phospholipids, sphingolipids, sterols, and oxidized lipid derivatives in brain tissue and peripheral biofluids. Instead of single abnormalities, directional metabolic imbalance is indicated by pathway changes, including decreased sphingomyelin-to-ceramide ratios and decreased polyunsaturated phospholipids. Co-analysis of lipidomic, genomic, and proteomic data has shown the existence of metabolically different subgroups, which aids genotype stratified risk evaluation and the lipid responder phenotype concept. Protein-centered therapies are complemented by therapeutic strategies that focus on lipid homeostasis, such as the regulation of cholesterol efflux, sphingolipid metabolism, pro-resolving lipid mediators, and metabolic reprogramming. There is also emerging evidence that implicates peroxisomal dysfunction and compromised glymphatic clearance in interfering with lipid balance. Although this field of research has come a long way, the issues of proving causality, standardizing lipidomic techniques, and converting pathway signatures into clinically useful resources persist. Restructuring AD as a lipid network instability disorder offers a systems level model of earlier diagnosis and targeted treatment.
Balakrishnan et al. (Tue,) studied this question.